The main character is Gustav von Aschenbach, a famous author in his early fifties who has recently been ennobled in honor of his artistic achievement (thus acquiring the aristocratic "von" in his name). He is a man dedicated to his art, disciplined and ascetic to the point of severity, who was widowed at a young age. As the story opens, he is strolling outside a cemetery and sees a coarse-looking red-haired foreigner who stares back at him belligerently. Aschenbach walks away, embarrassed but curiously stimulated. He has a vision of a primordial swamp-wilderness, fertile, exotic and full of lurking danger. Soon afterwards, he resolves to take a holiday.
After a false start in traveling to Pula on the Austro-Hungarian coast, Aschenbach realizes he was "meant" to go to Venice and takes a suite in the Grand Hôtel des Bains on the Lido island. While shipbound and en route to the island he sees an elderly man, in company with a group of high-spirited youths, who has tried hard to create the illusion of his own youth with a wig, false teeth, makeup, and foppish attire. Aschenbach turns away in disgust. Later he has a disturbing encounter with an unlicensed gondolier—another red-haired, skull-faced foreigner—who repeats "I can row you well" when Aschenbach orders him to return to the wharf.
Aschenbach checks into his hotel, where at dinner he sees an aristocratic Polish family at a nearby table. Among them is an adolescent boy of about fourteen in a sailor suit. Aschenbach, startled, realizes that the boy is supremely beautiful, like a Greek sculpture. His older sisters, by contrast, are so severely dressed that they look like nuns. Later, after spying the boy and his family at a beach, Aschenbach overhears the lad's name, Tadzio, and conceives what he first interprets as an uplifting, artistic interest.
Soon the hot, humid weather begins to affect Aschenbach's health, and he decides to leave early and move to a cooler location. On the morning of his planned departure, he sees Tadzio again, and a powerful feeling of regret sweeps over him. When he reaches the railway station and discovers his trunk has been misdirected, he pretends to be angry, but is really overjoyed; he decides to remain in Venice and wait for his lost luggage. He happily returns to the hotel and thinks no more of leaving.
Over the next days and weeks, Aschenbach's interest in the beautiful boy develops into an obsession. He watches him constantly and secretly follows him around Venice. One evening, the boy directs a charming smile at him, looking, Aschenbach thinks, like Narcissus smiling at his own reflection. Disconcerted, Aschenbach rushes outside, and in the empty garden whispers aloud, "I love you!"
Aschenbach next takes a trip into the city of Venice, where he sees a few discreetly worded notices from the Health Department warning of an unspecified contagion and advising people to avoid eating shellfish. He smells an unfamiliar strong odour everywhere, later realising it is disinfectant. However, the authorities adamantly deny that the contagion is serious and tourists continue to wander round the city, oblivious. Aschenbach at first ignores the danger because it somehow pleases him to think that the city's disease is akin to his own hidden, corrupting passion for the boy. During this period, a third red-haired and disreputable-looking man crosses Aschenbach's path; this one belongs to a troupe of street singers who entertain at the hotel one night. Aschenbach listens entranced to songs that, in his former life, he would have despised – all the while stealing glances at Tadzio, who is leaning on a nearby parapet in a classically beautiful pose. The boy eventually returns Aschenbach's glances, and, though the moment is brief, it instills in the writer a sense that the attraction may be mutual.
Next, Aschenbach rallies his self-respect and decides to discover the reason for the health notices posted in the city. After being repeatedly assured that the sirocco is the only health risk, he finds a British travel agent who reluctantly admits that there is a serious cholera epidemic in Venice. Aschenbach considers warning Tadzio's mother of the danger; however, he decides not to, knowing that if he does, Tadzio will leave the hotel and be lost to him.
One night, a dream filled with orgiastic Dionysian imagery reveals to him the sexual nature of his feelings for Tadzio. Afterwards, he begins staring at the boy so openly and following him so persistently that Aschenbach feels the boy's guardians have finally noticed, and they take to warning Tadzio whenever he approaches too near the strange, solitary man. But Aschenbach's feelings, though passionately intense, remain unvoiced; he never touches Tadzio, or even speaks to him; and while there is some indication that Tadzio is aware of his admiration, the two exchange nothing more than the occasional surreptitious glance.
Aschenbach begins to fret about his aging face and body. In an attempt to look more attractive, he visits the hotel's barber shop almost daily, where the barber eventually persuades him to have his hair dyed and his face painted to look more youthful. The result is a fairly close approximation to the old man on the ship who had so appalled Aschenbach. Freshly dyed and rouged, he again shadows Tadzio through Venice in the oppressive heat. He loses sight of the boy in the heart of the city; then, exhausted and thirsty, he buys and eats some over-ripe strawberries and rests in an abandoned square, contemplating the Platonic ideal of beauty amidst the ruins of his own once-formidable dignity.
A few days later, Aschenbach goes to the lobby in his hotel, feeling ill and weak, and discovers that the Polish family plan to leave after lunch. He goes down to the beach to his usual deck chair. Tadzio is there, unsupervised for once, and accompanied by an older boy, Jasiu. A fight breaks out between the two boys, and Tadzio is quickly bested; afterward, he angrily leaves his companion and wades over to Aschenbach's part of the beach, where he stands for a moment looking out to sea; then turns halfway around to look at his admirer. To Aschenbach, it is as if the boy is beckoning to him: he tries to rise and follow, only to collapse sideways into his chair.
His body is discovered a few minutes later.