Flanigan was born Joseph Dunnigan III in Los Angeles, California. He has said that his father left his mother soon after he was born and that his surname was changed to Flanigan after he was adopted by his stepfather, John Flanigan. Flanigan has three brothers and four sisters. When he was six years old, his family moved to a small ranch near Reno, Nevada.

From the age of 14, Flanigan attended a boarding school in Ojai, California, where he appeared in the school's production of A Streetcar Named Desire. He later earned a history degree at the University of Colorado where he appeared in the play Coriolanus. On the advice of a friend, he took acting to overcome his shyness but did not plan to pursue a career in acting. As part of the Junior Year Abroad program, Flanigan spent a year studying at the Sorbonne in Paris, where he learned French.

After graduation, he pursued a writing career. He worked on Capitol Hill 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 had guest roles in numerous television series including Profiler, First Monday, and Sisters, until he got his breakthrough with his role on Stargate Atlantis as Lt. Colonel John Sheppard. He lived in Vancouver, Canada, where the series was filmed during the week, and flew to Los Angeles during the weekends where his wife and children reside. He additionally wrote for the series, and created the stories for the Stargate Atlantis second season episode "Epiphany" and the fourth season episode "Outcast".

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.

Flanigan appears in Brooks Institute photographer John A. Russo's upcoming book About Face.Part of the proceeds are to be donated to Smile Train.

Personal life
Flanigan has been married to Katherine Kousi, an actress and painter, since 1996. They have three sons: Aidan, Truman, and Fergus. They reside in Malibu.

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 is best friends with Stargate Atlantis co-star Jason Momoa which Momoa has said in many interviews. They often lived together while shooting the show in Vancouver, and they both lived in Malibu separately during season breaks, where they would surf together. He is also good friends with co-star David Hewlett.

He shares his birthday with former Stargate Atlantis co-star Paul McGillion.