In the opening shot, an eight-year-old overweight boy, named Billy (Jackson Nicholl), is sitting in the waiting room of a law office. He reads a magazine and turns to a page with a picture of a guy fishing. Billy turns to the lady next to him and says he'd like to live in that spot next to the jail house since his mom is going there for getting caught selling drugs. His mom then comes out to grab him and tell Billy they're going to see his grandpa.
We meet the enderly Irving Zisman (Johnny Knoxville) sitting in the waiting room of a hospital, checking out a magazine of his own and getting aroused at the sexual imagery. A nurse comes in to tell Irving that his wife had taken a turn for the worst, and she is now dead. After a brief moment of silence, Irving starts laughing, overjoyed that his wife is dead. He talks to his penis "Leroy" and says "We're free!" Irving leaves the hospital to get himself off, but unfortunately for him, the massage parlor and strip club are closed. Desperate, he sticks his penis in the slot of a vending machine. That's when he gets himself stuck and starts asking onlookers for help. He tries pulling his penis out, stretching it to an unnatural length before someone steps in to help.
Irving attends his wife Ellie's (Catherine Keener, as a corpse) funeral with a whole group of strangers. He is surprised to see them all though he admits he and Ellie outlived all their friends. Just as he starts giving a speech, Billy and his mom Kimmie (Georgina Cates) barge in and Kimmie pulls Irving out to talk to him. She has a loud conversation with him saying she's going back to jail for violating her parole, and she orders Irving to make sure Billy stays with his father. Irving reluctantly agrees and they re-enter the church. Kimmie starts to steal a pearl necklace from Ellie's casket, but Irving goes to stop her. Their struggle ends up pushing Irving into the casket, spilling Ellie's corpse onto the floor to the horror of everyone in attendance.
Irving takes Billy to a restaurant to meet with a counselor while they contact Billy's father Chuck (Greg Harris) via webcam to inform him of the current circumstances. Chuck turns out to be a deadbeat jerk who refuses to take Billy in as he cannot afford to. He proceeds to take a hit from his bong as his girlfriend comes in to remind him that he can get child support for Billy, so he instructs Irving to take Billy down to Raleigh, North Carolina to drop him off with Chuck by Sunday at 2:00.
Irving later starts selling Ellie's belongings. He tries to sell her bed to a potential customer and then offers to test it out. He hands her a pad with a button to adjust the bed, but once she presses it, the bed folds rapidly, bending Irving repeatedly. The customer is then too freaked out to buy the bed. Later, Irving calls a couple of unwitting guys to come help take the bed out, though he really asks them to help him and Billy carry Ellie's body to the trunk of his car, since he felt that she needs to be taken south to be buried properly. Though disturbed, the two men help them and then leave before they are implicated in a crime.
Irving and Billy hit the road not long after getting everything together. Billy says he's hungry, so Irving pulls over to a nearby market where a woman is selling food. He tries to hit on her while Billy goes on a kiddie ride outside the shop. He tells Irving that it's not working, forcing Irving to test it out. He ends up getting shot through the window as the ride springs off it's base, startling everybody else. Frustrated, Irving tries to ship Billy off to North Carolina in a box. He takes him to the post office, but because Billy keeps moving and speaking, the two women in the place open it and are shocked to find him in there. Before he can get in anymore trouble, he says he'll just take Billy back on the road.
Irving leaves Billy in the car as he goes to a rec center to play Bingo with other older folks. Irving starts to drink the ink from the markers before pulling out a margarita maker and blending drinks for everybody. He mentions that he visited a country where lemon juice was squirted on a man's penis to determine if he had a disease, then proving his being clean by squirting lemon juice on his own penis. Irving then proceeds to hit on the women there, making them laugh or repulsing them. Meanwhile, Billy leaves the car to walk around and stop an older gentlemen to get him to tie his shoe. He keeps him talking for a few minutes while trying to coax the man into adopting him.
The two stop in a supermarket when Billy gets hungry again. Irving takes food out from their containers and makes himself and Billy sandwiches, which is seen by the employees. A woman comes out to chastise Irving for eating without paying and criticize him for influencing Billy. Still, Irving gets Billy to smuggle some items and run from the manager, who yells at Irving even as he tries flirting.
The two pull into a motel for the day. They pull Ellie's corpse out of the trunk since Irving thinks it would be disrespectful to leave it in the car, all while another man watches them in displeasure. Irving then asks the man if he knows where there is a strip club around here so he can seduce a black woman. The man points him out to one and he leaves Billy in the room.
Irving goes to a club featuring male performers. He tells one of the dancers that he plans on waiting until the women are so aroused by the dancers for him to swoop in and make his move. He starts talking to a group of women, making them laugh despite is crass behavior. When the men start to dance, Irving jumps on the dance floor and pulls down his pants, revealing his balls that sag past his thighs. Everybody runs away while laughing in surprise and disgust.
Meanwhile, Billy leaves the motel room to find Irving. He goes to another strip club and then to an adult book store. The book store employee offers to watch him while they find his grandpa, and Billy tells her that she looks like a stripper, naming her Cinnamon. Irving eventually comes back home before they have to hit the road again.
As they near North Carolina, Irving tries to use Billy as bait to find a woman to hook up with. The women they speak to find Billy adorable, but they all turn Irving down. They drive to a diner where Irving drives the car into a large penguin statue, knocking it over and arguing with one of the employees about fixing it. In the diner, Billy asks why he has to stay with his dad when he doesn't like him very much. Irving insists that he has to go with him, and then he farts. They get into a gassy contest, which ends when Irving pushes too hard and sharts against a wall. They proceed to leave and later play some basketball while Billy asks Irving if he can take him fishing.
On another misadventure, Billy gets hungry yet again and Irving takes him to a church where a wedding reception is taking place. During a group photo, Irving swipes a glass of champagne, causing the whole tower of glasses to collapse, and he ends up falling on top of the table, spilling the cake on the floor. Billy seizes the opportunity to eat some of the cake.
Irving eventually drives Billy to a bar where they are meeting Chuck. Chuck is talking to a member of a biker organization called Guardians of Children, who help abused kids. Chuck explains that Billy will allow for him to get child support just as Irving and Billy walk in the door. Irving asks Chuck to make sure that Billy is well taken care of, though he rudely responds to Irving that he'll get the job done. Irving bids Billy farewell and they say they love each other, just as the GOC members watch the scene. As Irving leaves tearfully, one GOC member comes out to assure him that they'll keep their eyes on Billy. Irving drives away, but quickly starts to miss Billy and reminisces about their time on the road. He proceeds to turn the car around and drive back to the bar to get Billy back, just as Chuck is showing off his bad parenting by denying Billy any food in the place. Irving calls Billy to him, but Chuck prepares to fight the old man. The GOC members pull the two away from each other and allow Irving to leave with Billy while they hold Chuck off and warn him there will be trouble if he acts threateningly.
To celebrate their reunion, Irving and Billy crash a child beauty pageant after spotting a flyer for it on their road trip earlier. Billy gets dressed up as a girl and charms most of the judges, even though one reigning child champion and her mother note the unusual event of a girl being there with a grandpa. Billy dresses up as a sailor girl to put on a show while "My Bunny Lies Over The Ocean" plays. It appears cute until Billy rips off the outfit to reveal him wearing women's underwear and then put on a risque pole dance to "Cherry Pie". The other parents and girls are stunned, and Irving tops it off by walking onstage and throwing Billy dollar bills. His wig falls off and the two run out.
Irving drives up to a bridge where he and Billy finally get rid of Ellie's body by throwing it into the river. The two then proceed to fish, fulfilling Billy's desires.
During the end credits are outtakes and behind-the-scenes looks at Johnny Knoxville performing as Irving in the outrageous stunts, and the reactions of all the unknowing extras when the filmmakers pop out to inform them that they're shooting a movie.
The credits end with a dedication to the late Ryan Dunn.