London, 1969. Two out-of-work actors share a squalid flat in Camden Town. Coming down from an extended amphetamine high, Withnail complains bitterly about the cold and his lack of employment. After an argument about the washing up, Withnail resolves to tackle the rotting pile of dirty dishes. Eventually, the attempt is abandoned and after a brief walk in Regent's Park, Withnail covers himself in Deep Heat to ward off the cold. A search for alcohol produces nothing but lighter fluid, which Withnail drinks eagerly, then vomits on Marwood's shoes.

In the local pub, an Irish regular takes exception to the perfume Marwood has used to remove the smell from his shoes. After vainly pleading to save his own skin - to Marwood's horror - Withnail flees; Marwood follows.

They are visited by local drug dealer Danny, who leaves them with a prototype of his latest invention, and outlines his plans to go into the toy business. Withnail recklessly boasts he can handle Danny's most powerful drugs, but when Danny names his price, he backs down, to Marwood's relief.

Following Marwood's suggestion that they go on holiday, the pair visit Withnail's Uncle Monty, hoping to borrow his cottage Crow Crag. Monty regales them with tales of his theatrical past and his 'sensitive crimes' with men. Marwood is uncomfortable, but Withnail delightedly invents stories of his own thespian successes, while helping himself to the drinks cabinet.

The pair drive north, arriving at Crow Crag at night in the pouring rain. To ward off the cold, they burn furniture. In the morning, Marwood visits the local farm to buy food and fuel, but is met with a hostile reception by the farmer's mother. Eventually, the farmer passes in his tractor and agrees to bring some fuel, wood and a chicken.

The chicken arrives, alive. After summoning up the courage to kill it, they cook it in the ratchety oven while Withnail fruitlessly phones his agent. Returning from the village with supplies, they leave a gate open and find themselves confronted by a randy bull. Withnail escapes over a wall, leaving Marwood alone with the bull. On the advice of the farmer, Marwood runs screaming at the bull and chases it away.

At The Crow pub, Withnail charms the ex-services landlord with invented military exploits of his own. An attempt to buy food from a local poacher turns nasty when he takes exception to Withnail.

That night they hear noises in the cottage, and Withnail comes to Marwood's room, convinced it is the poacher. They cower together in the bed as footsteps climb the stairs and the door is opened, revealing - Monty. Withnail is furious.

The next morning, Monty evidently has designs on Marwood, to the latter's deep discomfort. But his hopes of making an escape back to London are dashed by Withnail, who is now enjoying himself and insists he wants to stay.

Monty takes the pair to Penrith to buy Wellingtons. He gives them money, which they spend in the pub, before causing a drunken scene in a teashop. Over dinner, Monty continues to flirt with Marwood.

That night, Withnail collapses into drunken sleep. Monty pursues Marwood to his room, where he attempts to force himself on him, revealing that Withnail told him that Marwood was homosexual. The terrified, naked Marwood has invent a story about Withnail's obsessive love for him to get rid of Monty.

In the morning, Monty is gone, leaving a pathetic letter of apology. A telegram arrives: Marwood has an audition. The two pack up to return to London. En route, Withnail drunkenly 'makes time' while Marwood sleeps, and they are picked up by police. Despite Withnail's attempt to beat a drunk driving charge by using Danny's invention, they are released.

Back in London, they find Danny and his friend, Presuming Ed, in their flat, smoking a huge cannabis joint. Marwood reveals that he has been offered a leading role. As they smoke more of the drug, they become deliriously high, while Danny details his philosophy and his legal ambitions.

Marwood packs to leave; Withnail insists on walking with him through Regent's Park. Marwood bids Withnail farewell, leaving him to recite Hamlet speeches to bedraggled wolves.