Shepard has appeared in the feature films Without a Paddle (2004), Zathura: A Space Adventure (2005), Employee of the Month (2006), Idiocracy (2006), Let's Go to Prison (2006), Hit and Run (2012), and CHiPs (2017), the last two of which he also wrote and directed.

He played Luke Matthews in the Netflix show The Ranch, co-starred in ABC's Bless This Mess and acted in the MTV practical joke reality series Punk'd (2003).

[13] He has an older brother, David Shepard Jr., who lives in Oregon,[7] and a younger half-sister, Carly Hatter,[3] whom he cast in two films: 2012's Hit and Run[14][15] and 2017's CHiPs.

[16] Shepard has said that he was raised in Milford,[3] although he lived in a lot of places in suburban Detroit, growing up primarily in Walled Lake, Michigan.

[3] He found out about The Groundlings improv troupe from a friend from Santa Barbara, Kareem Elseify, who ended up auditioning (the first time he acted) and took classes while attending UCLA.

After about five years of classes, he got into the Sunday Company of The Groundlings—in a group that included Melissa McCarthy, Fortune Feimster, Tate Taylor, and Nat Faxon.

In 2006, he appeared with Dane Cook and Jessica Simpson in the comedy Employee of the Month and in Mike Judge's film Idiocracy as the character Frito.

During the same time, Shepard began appearing in more films and landed his first main character role in Let's Go to Prison (2006), alongside Will Arnett and Chi McBride.

[22][23][24] Shepard wrote, produced, co-directed, and starred in the 2012 low-budget film Hit and Run alongside Bell and his close friend Bradley Cooper.

Featured guests on the show have included Barack Obama, Bill Gates, Kristen Bell, Ashton Kutcher, Will Ferrell, Julia Louis-Dreyfus, and hundreds of others.

Featured experts on the show have included psychologist Wendy Mogel, comedian and author David Sedaris, and speechwriter Jon Favreau.

[36] Shepard met actress Kristen Bell, also a native of Detroit's northern suburbs, at the birthday party of a mutual friend; they began dating in late 2007.

[37][38] After section 3 of the Defense of Marriage Act was ruled unconstitutional by the Supreme Court on June 26, 2013, Bell asked Shepard through Twitter to marry her,[39] which he accepted.

[3] On September 25, 2020, in a special episode of his podcast, Armchair Expert, Shepard revealed he had relapsed while recovering from an accident by using painkillers to augment a prescription.

He has served as their official Master of Ceremonies, along with his friend Tom Arnold, for the Inner-City Games and Hollenbeck Youth Center's Miracle on 1st Street Toy Giveaway Program in East Los Angeles.