After graduation, he pursued a writing career. He worked on Capitol Hill on President George H.W. Bush advanced team. and then briefly for several New York City publications, including Town & Country and Interview magazine. On the advice of some of his friends, he studied at the Neighborhood Playhouse, was coached by Gerald Gordon, and then moved back to Los Angeles in 1994 to pursue an acting career.

Flanigan married Katherine Kousi, an actress and painter, in 1996. They have three sons. In early 2014, it was announced they had separated.

Flanigan took two prizes in the Waterkeepers’ Alliance downhill skiing competition at Lake Louise in January 2006, an event fellow Stargate lead Richard Dean Anderson has attended as well. He currently resides in Malibu, California. On November 10, 2018, the Malibu home he was renting from a local family was lost in the Woolsey Fire.

In September 2007, scifi.com’s SciFi Wire service reported that, “Talent agency UTA filed suit on Sept. 24 against Stargate Atlantis star Joe Flanigan in Los Angeles Superior Court, claiming that the actor owes $99,225 in commissions, according to The Hollywood Reporter; Flanigan’s manager, John Carrabino, told the trade paper about the lawsuit: ‘I had no idea they did this. This is the first time I’m hearing about this.'” UTA filed a similar lawsuit against actor Wesley Snipes who was equally surprised. This suit was settled in December 2008.

In 2019, Flanigan joined the cast of General Hospital as recurring character Dr. Neil Byrne.