Aspiring comedian Pete finds himself without a home after he catches his wife, Jessica, in a compromising position. As Pete attempts to find solace at a New York comedy club, he befriends cynical comedy legend Artie Lange, who reluctantly offers him some pizza, some advice and a couch.
Pete wallows in his new reality, but Artie Lange snaps him out of it with an offer: In exchange for a ride to Albany, Pete can be Artie's opening act. Pete meets co-headliner T.J. Miller and attempts to save Artie from breaking his sobriety by getting between him and the temptations of an ardent fan.
While staying at T.J. Miller's place, Pete has the unsettling experience of witnessing a comic who can't "turn it off". Hearing from his wife, Jessica, Pete and T.J. travel upstate to her yard sale, where Pete unexpectedly teams up with Jess' new boyfriend, Leif, to get back a prized possession. After Jess voices her true feelings to Pete, the sale comes to a dramatic end.
In an effort to get stage time, Pete spends the night handing out fliers for a comedy club, or "barking", as he later learns it's known in the comedy world. On the streets of New York, he finds himself encountering disinterested locals, befriending up-and-coming comics, engaging in a turf war with a rival barker and getting a pep talk from a veteran comedian.
When Pete's parents decide to come to New York for his mother's birthday, Pete begs Jess to come along and keep up the charade of their marriage, but an incredibly tense dinner reveals harsh truths about their relationships, as Jess struggles to keep quiet. Pete faces a turning point.
Homeless once more and facing professional disappointment, Pete turns to Artie Lange, who invites him to be a guest on his podcast. Pete meets Sarah Silverman, who takes pity on him and invites him to stay with her and her collection of stray comedians. When Sarah suggests that he try to find work as an audience "warm-up" comedian, Pete is presented with a job opportunity, where he's tasked with saving the day.
Pete's high from his new warm-up gig on Rachael Ray's show is interrupted by an unexpected visit from Leif's wife, who pulls him back into the chaos of his separation from Jess.
After an attempt to cheer up Pete goes wrong, Artie tags along with him to a baptism. Artie gets insight into religion and God from a woman, and Pete runs into Jess, which makes him question how much he is willing to sacrifice for a life in comedy.