A Confederacy of Dunces recounts the adventures of Ignatius J Reilly of New Orleans, a mammoth of a man and a martyr to trapped wind who is engaged in a Quixotic running battle against pretty much anything that the modern world can come up with.

The book is peopled with interconnecting characters whose lives are buffeted and disrupted by Ignatius as he fights "offenses against taste and decency" and laments the general "lack of theology and geometry". 

He lives with his mother, spending most of his time in his fetid bedroom or screaming his disapproval at light entertainment TV shows. But when his mother crashes the family car, smashing up a front porch, the cost of damages means that Ignatius must go out and find work. 

Taken on as a filing clerk at Levy Pants, Ignatius sets about imposing his worldview and attempting to provoke the jealousy of his activist ex-girlfriend Myrna Minkoff. He introduces several eccentric innovations around the office and on one occasion writes an abusive letter in Mr Levy's name to an important distributor. Ignatius leads a revolt of his co-workers in pursuit of higher pay. But his so-called "Crusade for Moorish Dignity" quickly breaks down and he is sacked.

His next job as a hot dog vendor brings him into contact with George, who turns out to be a runner for a porn racket run by Lana Lee, the owner of the Night of Joy bar and strip club. George persuades Ignatius to let him rent the bun compartment of the hot dog cart as a place to store packages. Ignatius opens one of the packages to find a lewd picture of a woman posing on a desk in a study apparently reading The Consolation of Philosophy. Impressed, he determines to track the woman down by going to the address on the package.

This turns out to be the Night of Joy, which happens to be the bar into which, a few nights earlier, Ignatius and his mother had fled after an altercation with a patrolman called Mancuso, and from which they were ejected as drunkards. Lana Lee sees Ignatius outside reading a poster for a forthcoming show by Harlett O'Hara and persuades her disgruntled doorman Burma Jones to go and get rid of him. To spite his boss, Jones tells Ignatius that Harlett is the woman he is looking for and invites him to the opening night.

When, later that week, Ignatius makes his way to Harlett's show, his trail is picked up by the now undercover patrolman Mancuso. Much to his disgust, Harlett turns out to be only an exotic dancer called Darlene rather than the devotee of philosophy he had been expecting.  When he bellows his disapproval, Ignatius is attacked by the cockatoo that is part of Darlene's stage act and a riot ensues. He staggers from the bar into the path of an oncoming bus where he faints, only to be pulled clear by Burma Jones.

Ignatius wakes up in hospital and reads newspaper reports and pictures of the previous night's incident. He learns that patrolman Mancuso had turned up after he had left and was able, with the help of Jones, to bust the porn racket.

On returning home with his mother, they find Mr Levy on their doorstep with a threatened $500,000 libel suit from the distributor that Ignatius had berated in his letter from Levy Pants. Although the situation is solved when Ignatius shifts the blame for the letter to Miss Trixie, an elderly employee of the company, Mrs Reilly secretly decides to have Ignatius admitted to the Charity Hospital.

He gets wind of her plan and is just getting ready to escape when Myrna Minkoff arrives. They quickly gather all his things, jump into her car and drive away just as the Charity Hospital ambulance pulls up.