The novel opens with a Prologue describing the depressed state of the narrator, who remains nameless throughout the novel. He is an invisible man, he proclaims, and has taken to living unknown underground, sucking electricity from the state of New York into his many light bulbs that he has hung in his lair. The novel is to be the story of how he came to be in this position.
As a young boy, the narrator overhears the last words of his dying grandfather, whose message lingers with him through high school. He is struck with this idea when he is asked to give his college oration to the town's most honored white men. At the fancy ballroom where he attends the occasion, he is ushered into the battle royal with the other boys hired for the evening's entertainment. First however the boys are brought into the room where a naked woman dances. The boys are next blindfolded and pitted against each other in a boxing ring. After several fights, only the narrator and the largest boy, Tatlock, remain and they are told they must fight each other for a prize.
The next stage requires the boys to grab for gold coins on a rug which turns out to be electrified. The narrator is finally allowed to give his oration and is awarded a scholarship to a renowned black college. At college, he is first faced with the disillusionment which will overcome him by the end. The memory is painful as he relates the day he was given the honor of driving an old white trustee, Mr. Norton, around the campus. The drive goes smoothly for a while although Mr. Norton's questions surprise the narrator. Norton sees every student at the college as part of his fate. He also welcomes a chance to explore parts of the surrounding town . Mistakenly, the narrator drives Norton into a poor district of black sharecroppers and Norton is intrigued by a disgraced member of the community, Jim Trueblood, who is rumored to have impregnated both his wife and daughter. Trueblood gives a long description of the dream which made him commit the act of incest and resulted in his wife trying to kill him. After this episode, Norton feels faint and the narrator takes him to the Golden Day brothel in order to find whisky to revive him. Mental patients visiting the bar unfortunately rise up against their attendant, trapping the narrator and Norton in the middle of the fight. Falling unconscious, Norton is revived by a former doctor who speaks to him of the narrator's invisibility. Thinking the doctor insane, he and the narrator finally return to the college where the narrator is punished for his treatment of Mr. Norton. The college president, Dr. Bledsoe, relates to the narrator that he should have only showed the trustee what the college would have wanted him to see. The narrator is expelled and sent to New York with seven sealed letters to wealthy employers with the promise that he can return as a paying student in the fall. Though stunned, the narrator decides to take advantage of the opportunity to work for an important person in New York City.
Arriving in Harlem, he is dazed but excited. He rents a room at the Men's House in Harlem and sets out the next morning to start handing out his letters. That process goes smoothly although he is only able to give the letters to secretaries and is told the employers will contact him. After not hearing anything, the narrator becomes suspicious of the secretaries and holds the last letter back, asking first to meet with the employer, Mr. Emerson, upon which he could personally give him the letter. The narrator's efforts are once more interceded, though, as Mr. Emerson's son takes the letter from him at the office and attempts to talk him out of returning to the college or speaking to his father. Finally, the son finally shows the narrator the letter from Dr. Bledsoe which the narrator had been told not to look at. The narrator is horrified to read what is written. Bledsoe writes explicitly to the employers that the narrator will never be allowed back to the school and asks them to see to it in the meantime that he will not be able to return to school as a paying student. Disillusioned, the narrator leaves the office utterly humiliated and terribly angry. He decides to take a job at a paint factory in order to be able to plan out his revenge on Dr. Bledsoe.
The idea of revenge is jumbled during the one long day he spends working at the paint plant. His boss, Mr. Kimbro, is very brusque and demanding, putting the narrator immediately on the job with very few instructions and the order not to ask questions. When the narrator mixes the wrong ingredient into the paint because he is afraid to ask Kimbro, he is fired from that job and handed to another boss, Mr. Brockway, who works as the engineer of sorts. Brockway is paranoid that the narrator is trying to take his job and is thus quite irritable toward him, asking him many questions about his past. They get along agreeably enough until after the narrator returns from retrieving his lunch. In the lockerroom he had run into what he thinks is a union meeting, though we later realize it was a Brotherhood meeting, and it had delayed him. He explains this to Brockway who explodes in anger at his participation in a union and attacks him, refusing to listen to the narrator's explanation. The narrator feels the tension snap inside him and fights off Mr. Brockway. Because of their inattention to the gauges in the room, the tanks burst from the pressure and the narrator is covered in white paint and knocked unconscious.
He swims in and out of consciousness for what seems like days in a plant factory, surrounded by doctors who speak of lobotomies and tests which they would not try on him if he had been a white Harvard student. Desperately clutching consciousness at one point, he is asked his name but is unable to remember it. Finally, the doctors release him from the tubes and machines, saying that he has been saved though he never really knows from what. He is brought to the hospital director before he can leave, where he is told that he can no longer work at the plant but will receive ample compensation. Still foggy, he stumbles back toward the Men's House where he is relieved on his way by a strong, motherly woman named Mary Rambo. The narrator hesitantly agrees to let her take him back to her house where he can rest and revive his spirits. She feeds him and also offers him a place to stay before he returns to the Men's House. Returning to the house after his hospital stay and lowly employment, he feels inferior and realizes he can no longer reside there. After offending a man he first believes is Bledsoe, he is thrown out of the House and takes Mary up on her offer.
Able to pay rent with his compensation money, the narrator lives with Mary for a while in relative quiet. Once the winter comes to New York, the narrator feels restless and takes to wandering streets, still filled with rage toward Bledsoe. After reconnecting with his own identity by eating southern yams sold on the street, he is drawn to an eviction where an old black couple is being thrown out into the cold. A crowd has formed around the defenseless couple who shriek and cry out against the injustice. The scene of dispossession strikes the narrator to the core and he begins to speak to the crowd after the couple is denied the chance to go inside their home and pray. His emotions clashing, he stands in front of the crowd calming them and forming their chaos into an ordered rage. Once the crowd rushes the house, the narrator runs to escape lest the police come after him. Running over rooftops, he is followed by a short man who later approaches him on the street. The man introduces himself as Brother Jack and praises the narrator on his moving oration. He offers him a job with the Brotherhood, taking advantage of his speaking skills. Brushing aside the offer, the narrator later reproaches himself for not getting more details about the job when he is in such debt to Mary. He decides to accept the job in order to pay back Mary, but must stop living with her once he is accepted into the Brotherhood. His first glimpse into the organization is at the party/meeting they bring him to at the Chthonian Hotel. The upscale, mostly white crowd makes him uncomfortable but they all appear friendly and praise his action at the eviction. Brother Jack explains to the narrator that his role will be one of leading the community of Harlem in line with the Brotherhood's teachings, in the manner of Booker T. Washington. Secretly, the narrator vows to follow the example set by the college's founder instead.
The narrator leaves Mary's house the next day. In his room that morning, he finds a piggy bank in his room shaped offensively like a black man with overly exaggerated features. After breaking it by accident, he attempts to get rid of it but cannot. He is then sent to Brother Hambro for training, given a new apartment, and a new name. After completing training, the Brothers call him down to Harlem and he is shown the office where he will work, along with Brother Tarp and Brother Clifton, the handsome youth leader. He quickly becomes accustomed to his new work, relishing the ability to inspire the community around him. He and Clifton meet up with Ras the Exhorter, who competes with them for the community's support and chastises them for being traitors to their African race. The two groups fight until the narrator leads them away. Still the narrator feels secure and powerful in his position until he receives an ominous note warning him to move slowly and carefully. Alarmed, he questions Brother Tarp to see if he has any enemies. Tarp reassures him and opens up to him, relating painful parts of his past and giving to him a broken link he has saved from breaking away from a chain gang after nineteen years. Brother Wrestrum also visits on the day of the mystery note, and incites suspicion with the narrator because he seems meddlesome. His idea for a Brotherhood emblem is overshadowed by his attack on the inherently symbolic message of Tarp's chain link. The narrator agrees to be interviewed by a Harlem publication after trying to get them to speak to Clifton.
Weeks later, the narrator is called by the Brotherhood committee to an urgent meeting where he is charged by Wrestrum for attempting to overshadow and dominate the Brotherhood, naming some unknown plot against the Brotherhood and using the article the narrator was interviewed for as evidence. Until the accusations are cleared, the narrator moves downtown to speak on the Woman Question. Frustrated by the move but willing to try it, he meets a married woman who seduces him. The affair stays with him though he does not see her again, as he is frightened that the Brotherhood will find out and use it against him. Soon he is summoned to another emergency meeting which alerts him to Clifton's disappearance and reinstates him in Harlem. Returning to his old post, he finds that much is changed in the short time he has been gone. Tarp and Brother Maceo are gone as well and the spirit in the district is much subdued, as many of the people feel that the Brotherhood has let them down. Realizing he is now out of the Brotherhood loop, he plans to revive the neighborhood sentiment on his own. By chance, he finds Clifton further uptown where Clifton has become a street seller of a dancing, paper Sambo doll. Disgusted and intrigued, the narrator watches the performance and the police chase which follows, ending in the unnecessary killing of Clifton.
He decides to hold a funeral which can serve to unite the community of Harlem around a fallen hero of sorts. Though successful, the Brotherhood is outraged and meets him back in his office, at which point Jack angrily reveals that he has not been hired to think. They order that he continue in the district and send him to Hambro in order to understand the new, less aggressive program.
Thoroughly changed by Clifton's fate and the recent events, the narrator feels very angry toward the Brotherhood and walks around the neighborhood to think. He notices that the district is much more stirred by Clifton's shooting than he had presumed and he is drawn in by Ras to explain the Brotherhood's limited action following the murder. He defends their position and then moves away to buy a disguise so he will not be harmed by any of Ras's men. Surprisingly, due to dark green glasses and a wide hat, people begin to approach him and refer to him as Rinehart. He is able to go unnoticed by Ras but is constantly noticed by others as Rinehart, by lovers and zoot-suiters. Going back to a bar he normally frequented, he is still mistaken for Rinehart and is almost swept along into a fight with Brother Maceo. Later, on the way to Hambro's, the narrator uncovers a church where Rinehart is a reverend. His many identities and obvious manipulation of people's faith disturbs the narrator greatly and he approaches Hambro even more cynical than the Brotherhood left him. Hambro attempts to indoctrinate him into the new program, describing the scientific logistics, but to no avail. The narrator feels he can finally see how the Brotherhood and so many organizations in his life have swindled and manipulated their constituents. Resolved to attack the Brotherhood from the inside, he plans to "yes" the white men to death, referencing his grandfather, and to find a woman whom he can seduce into giving him inside information.
He chooses Sybil as she is vulnerable and married to an important brother, however she surprises him by wanting him to rape her. He escapes the situation when he is called uptown to Harlem for a crisis, although she attempts to tag along. A riot is in action and the narrator is swept along with it, nearly shot, and aids in the arson of an apartment building. The climax of the riot occurs when Ras rides through on a black horse dressed as a chieftain and wants the narrator hanged. Running from Ras' goons, the narrator falls down a manhole and realizes that he must live underground for awhile. The Epilogue is his resolution to reemerge into the world of social responsibility.