A Confederacy of Dunces presents the misadventures of Ignatius J. Reilly, a modern Don Quixote. Ignatius is a behemoth of fat and flatulence, with a gargantuan frame, bushy black moustache, green hunting cap, and blue and yellow eyes that look down on the modern era--and particularly on anything commerical. He views materialistic comforts as "offenses against taste and decency," things that demonstrate a lack of "theology and geometry."
His troubles (or fateful fortunes) begin in New Orleans when an inept patrolman suspects him of being a pervert and attempts an arrest. Ignatius is able to avoid being taken into custody, but as people help him, a kind grandfather who stood up for him is taken to jail. Fleeing the scene, Ignatius and his mother head to Bourbon Street and stop off in the Night of Joy, a bar and strip club, where they receive terrible service. Mrs. Reilly throws back drink after drink, while Ignatius tells the tale of his awful trip to Baton Rouge (the only time he has left New Orleans).
Meanwhile, at the police precinct, Claude Robichaux (the old man who helped Ignatius) has been placed on a bench with a young, black man wearing space-age sunglasses. This man is Burma Jones, and he has been falsely accused of stealing cashew nuts. When the police sergeant learns that Patrolman Mancuso has arrested a grandfather and was trying to apprehend Ignatius (a boy simply waiting for his mother), the sergeant punishes the inept officer: he must wear a new, ridiculous costume each day.
Having been thrown out of the Night of Joy by its tyrannical proprietress, Lana Lee, Ignatius and his mother return to their Plymouth. A wet spot in the road (combined with the distraction caused by Ignatius's incessant complaints from the back seat) causes Mrs. Reilly to crash into the side of a building, bringing a balcony crashing down on the car.
As a result of the car accident, Mrs. Reilly owes more than a thousand dollars for the damage. This debt, plus the payment that she must make each month for Ignatius's trumpet, is far more than she can afford, and she fears that she will be locked up for defaulting. Though Ignatius seems indifferent to the situation, Mrs. Reilly forces him to leave the comforts of his bedroom to enter the working world.
Ignaitus obtains a filing position at Levy Pants, a job that he finds surprisingly agreeable. Ignatius introduces a number of innovations to the office, such as arriving to work an hour late (thereby ensuring he is refreshed when he gets there) and throwing the filing in the garbage (creating more space in the filing cabinet and avoiding a fire hazard). He is quite fond of his coworker, Miss Trixie, a senile, old assistant accountant who wants nothing more than to retire from Levy Pants. Ignatius is so pleased with his new employment that he dedicates himself to raising the firm to the next level of success. According to Ignatius, the first thing the company needs to do is be more authoritarian with its distributors. Toward this end, he writes a letter on behalf of Mr. Levy (without his knowledge or permission) to a Levy Pants distributor, Abelman's Dry Goods, that has complained about a defective batch of pants. Ignatius's letter to Mr. Abelman calls him a mongoloid and threatens to lash him should he bother Levy Pants again.
The most important aspect of the job is that it provides the means for avenging Myrna Minkoff's latest effrontery. Myrna is an ex-girlfriend from college with whom he corresponds regularly. In her letters, Myrna accuses him of paranoid delusions, which she attributes to the total failure of his life. Moreover, she often suggests that he has homosexual tendencies. In efforts to make Myrna jealous, Ignatius plans to lead a social movement of historic proportions. Specifically, he convinces the Levy Pants factory workers to participate in a demonstration against the Levy Pants office manager, Mr. Gonzalez, demanding higher wages. Ignatius titles the protest the "Crusade for Moorish Dignity," and he leads the workers into the office as they sing spirituals. The demonstration quickly falls apart, however, when news spreads among the workers that Ignatius may have a police record, and when Ignatius orders the workers to attack Mr. Gonzalez without even giving him the opportunity to respond to the demand for higher wages (this tactic they find very unfair and a confirmation that Ignatius probably is a criminal). Rather than achieving a victory for social justice that he can slap in Myrna's face, he ends up unemployed.
Mrs. Reilly insists that Ignatius enter a new job search. He soon gets employment as a hot dog vendor for Paradise Vendors, Incorporated, a job which his mother finds incredibly humiliating. Ignatius brings in few profits as a vendor--he spends more time eating than selling the products. In an attempt to bring in more revenue, Ignatius's employer, Mr. Clyde, reassigns him to the French Quarter (where there are more tourists) and has Ignatius dress in a pirate costume.
One day on his hot dog route, Ignatius runs into Dorian Greene, a flamboyant homosexual who throws extravagant counterculture parties. In talking to Dorian, Ignatius develops a new plan for social activism. He believes that if homosexuals infiltrate the armed forces and highest offices of countries around the world, war can be replaced with orgies and world peace can be achieved. He proposes that they form a political party and start running candidates immediately, including a kickoff rally. Dorian agrees to host the event.
Later, Ignatius runs into George, an oily-haired, pimply teen with flamenco boots. Lana Lee from the Night of Joy is running a high school pornography racket on the side, and George is her delivery boy, selling her product to orphans around the city. Each day at one o'clock, George picks up packages containing the pornography, and he delivers them to the orphans at three o'clock. He thus needs a place to store the packages for the two hours between pickup and delivery, so he offers Ignatius a couple of dollars per day in exchange for renting out the bun compartment in his hot dog cart as storage space. Ignatius agrees but then grabs one of the packages and tears it open to see what is inside. He finds a picture of a nude woman (Lana Lee) on a desk beside a globe, doing something suggestive with a piece of chalk. The woman's face is covered by the book she is "reading," Boethius's The Consolation of Philosophy (Ignatius' favorite work of literature)--and he immediately commends the woman's taste and brilliance. Seeing that an address is written on the package, he decides to investigate in order to identify this brilliant woman.
Thus Ignatius arrives at the address written on the package and is dismayed to learn that it is the Night of Joy. Outside the bar, his attention falls on a poster advertising a show that the Night of Joy will be presenting, starring Harlett O'Hara (who is really Darlene, an aspiring exotic dancer who works at the bar) and her pet cockatoo, which Darlene has trained to yank at rings attached to her dress, thus ripping off her clothing. Seeing Ignatius on the curb outside her establishment and fearing that his presence will somehow ruin her investment, Lana Lee sends Jones (whom she has hired as a porter at well below minimum wage through threats of reporting him to the police for vagrancy) to get rid of Ignatius. Hoping to locate the sexy scholar pictured in the photograph, Ignatius asks Jones whether the Night of Joy employs a woman who is given to reading. Jones tells him that Harlett O'Hara is the woman he is looking for. Throughout the novel, Jones has been complaining of the abuse he is suffering at Lana's hands, and knowing how much she disdains the fat kook in the green hunting cap, he sees this as a perfect opportunity for sabotage. He informs Ignatius that Harlett O'Hara's routine will be opening in a few days, and he invites him back for a ringside table at the show.
A few days later, dressed in his Paradise Vendors pirate suit and with a speech prepared, Ignatius heads to Dorian Greene's residence for the kickoff rally for his new "degenerate" political party. When he arrives at the party, however, he finds that the attendees are more interested in debauchery than in the critical issues of the day or in devising a plan for infiltrating the world's armed forces. When Ignatius shuts off the party's music and attempts to address the crowd, he is met with cries of disapproval and a barrage of verbal insults. The music resumes, the partygoers ignore Ignatius, and he finds himself under attack by three lesbians who rent an apartment in Dorian's building. Ignatius is promptly removed by force. As he leaves, a man in a silk suit and homburg hat emerges from the shadows and follows him.
Ignatius's bad luck continues. He goes to the Night of Joy for Harlett O'Hara's opening performance but learns that Miss O'Hara is merely Darlene. When he bellows in disapproval, Darlene's bird launches toward his head and latches onto the gold hoop earring that he is wearing. Ignatius jumps up, lashes his arms wildly at the bird, and in the process knocks over tables, smashes a champagne bottle, and ruins the show. Stumbling out of the bar past Jones, he steps into the path of an oncoming bus. Ignatius faints, and Jones pulls him out of the way at the last second. The man in the silk suit emerges and takes control of the situation. When he asks Lana Lee if he can use her phone, she propositions him and shows him one of her nude pictures. The man announces that he is the undercover officer Mancuso, and he arrests her for possession of pornography. Just then, the three lesbians from Dorian's party arrive and assault the patrolman.
Ignatius awakes in the hospital and finds that his mother is quite humiliated by the top story in the day's newspaper. As the article and photos reveal, after the bird attack on Ignatius, Officer Mancuso had arrested Lana Lee for soliciting and for possession of and posing for pornography. Additionally, he arrested the three lesbians for assault. Jones had then taken Mancuso to the cabinet under the bar, where they found packages of pornography and a list of names, thus cracking the most active high school pornography racket in the city. As a result of the chaos at the Night of Joy, Darlene and Jones find themselves out of work. Darlene, however, gets an offer from a bar owner who is attracted by all the publicity she got.
After returning from the hospital, Ignatius and Mrs. Reilly find that Mr. Levy is waiting outside their house. Mr. Abelman has threatened a libel suit for $500,000 due to the letter that Ignatius had written while still employed at Levy Pants. When Mr. Levy asks if he is the author of the letter, Ignatius denies any responsibility. Instead, he pins blame on Miss Trixie, who hates Levy Pants for the company's refusal to retire her. When Mr. Levy goes back to Miss Trixie and confronts her with Ignatius's accusation, she confesses (she remembers how nice Mr. Reilly had always been to her, does not think he would lie, and notes that there is plenty she cannot remember anyway). As a result, Ignatius's lie is able to save Mr. Levy from a libel suit, himself from prosecution for forgery, and Miss Trixie--giving her the retirement she has desired for so long.
Unaware of Miss Trixie's confession and fearing that Ignatius has gotten himself into serious trouble with this letter to Abelman, Mrs. Reilly decides to have Ignatius committed at Charity Hospital. Figuring out what his mother plans for him, Ignatius decides to attempt an escape. Just then, Myrna Minkoff arrives on his doorstep. Fearing that he needed more help than just a letter, Myrna had driven all night to get to Ignatius. Telling her that he has finally accepted his problems and is ready to do something with his life, Ignatius convinces Myrna to help him flee immediately. They gather his belongings, jump into the car and drive away, just as an ambulance with the words "Charity Hospital" on the side drives up.