The film begins with Gerry (Ben Mendelsohn) engrossed in listening to a captivating recording about poker 'tells' as he prepares to enter a high-stakes poker tournament at a flashy casino. Soon, he crosses paths with Curtis (Ryan Reynolds), who immediately makes a splash by winning the first hand handsomely and showing friendly interest in Gerry. Later, the story unfolds in a bustling bar where Gerry and Curtis share drinks, leading to the blossoming of their friendship. Curtis mentions he's off to New Orleans the very next day, and the plot takes a twist when Gerry finds himself waking on Curtis's girlfriend's couch.
After a call from Curtis, Gerry is persuaded to meet him at a dog track, where fortune smiles upon them and they strike it big. However, Curtis indicates a desire to leave, but Gerry convinces him to stay, resulting in Gerry losing all their winnings. In later interactions, Curtis shares a cautionary tale about quitting while ahead, yet somehow entices Gerry into a significant bet on a game of pool, revealing Gerry's apparent struggle with compulsive gambling.
The situation intensifies when Gerry meets Sam (whose actor is not provided), who seems intent on collecting a hefty amount of money that Gerry owes, threatening him to send a "Tim" that instills palpable fear. Later that night, Curtis reaches out to Gerry again, sharing that he won some tickets, which convinces Gerry of his luck turning. Gerry convinces Curtis to back him financially for a trip from St. Louis to New Orleans, believing that this venture will help him secure the $25,000 entrance fee for the tournament Curtis is aiming for in their destination.
They embark on a journey to a riverboat in St. Louis, where Curtis rekindles a connection with a waitress he hasn’t seen in several months. While Gerry hits a winning streak at the tables, his attempts to place phone bets are thwarted due to his debts. The duo makes their way to Memphis where Gerry is distracted from listening to the poker 'tells' recording by Curtis. They later venture to a dog track in West Memphis, with Curtis enjoying the nightlife while Gerry faces defeat in poker. A threatening text from Tim leads Gerry to fabricate claims of a $7,000 win, but their path leads them to Little Rock to visit Gerry's ex-wife, resulting in an unfortunate encounter.
Their journey continues to a casino in Tunica, Mississippi, where an escalating conflict arises as Gerry throws a fit about money for a room. Curtis figures out the deeper issues when Gerry admits that he's lost money in Memphis. After Curtis steps in to rescue Gerry from some unruly punks, they press on towards New Orleans, even pawning their belongings to fund a bet on a horse that ultimately fails. Their paths diverge when Curtis wins secretly on a different horse and meets with his mother, leaving her the remnants of his winnings.
Meanwhile, Gerry, spiraling into the New Orleans game, grapples with his diminishing luck until he unexpectedly starts a winning streak at a casino. When Curtis appears, he encourages Gerry to bet all he has, which leads to a staggering win of half a million dollars! In a shocking twist, Gerry departs that night with half the money, keeping his win a secret from Curtis.
