When he was 19, Goggins moved to Los Angeles to pursue a career in acting. He worked on a valet car parking service for various restaurants in the valley and sold cowboy boots. In 1990, after working in a few acting roles in Georgia, he got his first big break in Murder in Mississippi. While filming, Goggins met and became friends with Ray McKinnon, who played his father in the film, and with whom he began a creative partnership that continues. Goggins played Detective Shane Vendrell in the FX series The Shield. Goggins and McKinnon formed their production company Ginny Mule Pictures, which produced four films: The Accountant, Chrystal, Randy and the Mob, and That Evening Sun. Goggins and McKinnon also created the series Rectify. Goggins was set to play the lead and AMC had bought the pilot script, written by McKinnon, a role which went to Aden Young when the series later went to SundanceTV. Goggins played Boyd Crowder in the pilot episode of the FX series Justified, and was a recurring cast member in the first season of the show, while also shooting a major supporting role as a deadly death row inmate being hunted by the titular antagonists in the film Predators. In May 2010, his role was promoted to the main cast for the second season. In May 2011, he appeared in "Code of the West", a commercial for Ram Truck's "Guts & Glory" campaign. He appeared in Cowboys & Aliens as Hunt, a bandit formerly in the employ of the protagonist. In July 2011, Goggins was nominated for a Primetime Emmy Award for Outstanding Supporting Actor in a Drama Series for his role on Justified. He portrayed Billy Crash, a sadistic overseer and slave fighting trainer, in the 2012 film Django Unchained. From 2012 to 2013, Goggins guest-starred as transgender prostitute Venus Van Dam in the FX series Sons of Anarchy. He previously worked with the show's creator, Kurt Sutter, when the latter was a writer and executive producer on The Shield. The name "Venus Van Dam" is a play on the undercover name "Cletus Van Damme" used by Shane Vendrell, the character Goggins portrayed on The Shield. He played Chris Mannix in The Hateful Eight and Lee Russell in the HBO series Vice Principals. The New York Times critic Mike Hale wrote, "Walton Goggins makes a habit of being the best thing about the television shows he’s in." Goggins plays the role of Wade, the lead character in the CBSsitcom, The Unicorn, which premiered in 2019. In 2020, Goggins voices part of the real crime podcast Deep Cover: The Drug Wars.
Goggins was married to Canadian Leanne Kaun, who owned a Laurel Canyon, California, dog-walking business; she died by suicide on November 12, 2004. Goggins married filmmaker Nadia Conners in August 2011. Their son, Augustus, was born February 2011. Goggins showcases some of his photography on a blog that he created when he took a sabbatical and traveled across India. He is active in various nonprofit organizations that range from environmental to humanitarian work, and he regularly attends Global Green USA events. Additionally, Goggins is a partner in a spirits company, Mulholland Distilling.