Will Ferrell based the appearance of Ashley Shaffer on that of wrestling legend 'The Nature Boy' Ric Flair.
Kenny Powers, the series' protagonist, is the name of a real-life American stuntman who attempted to jump a portion of the St. Lawrence River in a rocket propelled Lincoln Continental. The stunt was conceived by a Canadian stuntman, Ken Carter. When it came time to jump, he backed out, and the crew contacted Kenny Powers, who then attempted the jump, failing in a dramatic fashion.
A body double was used for the scene in the season 1 finale when April Buchanon flashes her boobs because actress Katy Mixon refused to go topless. She said she was afraid of what her father might say.
The creators offered Walton Goggins a role on the third season of the show, but it wasn't possible, due to scheduling reasons. However, Goggins would end up starring in McBride's other HBO show's Vice Principals as well as The Righteous Gemstones.
The show is named after the song "Eastbound and Down" by Jerry Reed. The show's creators initially weren't sure if they could keep this as the title without getting sued.