Eric Dane was born on November 9, 1972, in San Francisco, California, the older of two brothers. His father is an architect and interior designer based in San Francisco. His mother, Leah (Cohn), was a homemaker. His ancestry includes English, German, Finnish, Russian Jewish, and Austrian Jewish, and he had a Bar Mitzvah ceremony.

He was a good athlete in high school. There, he started amateur stage work by playing Joe Keller in Arthur Miller's "All My Sons", and realized that this was all he wanted to do.

He moved to Los Angeles and made his television debut in 1993 on The Wonder Years (1988). In his early career, he also played bit parts on the TV series Married... with Children (1987) (1995), Silk Stalkings (1991) (1996) and Roseanne (1988) (1996). He played medical doctors more than once, first appearing as a Dr. Cooper in Gideon's Crossing (2000). He was also recurring as Jason Dean in the hit show Charmed (1998). From 2006 until 2012, he appeared as handsome Dr. Mark Sloan, the plastic surgeon on the show Grey's Anatomy (2005). He is also starring as Tom Chandler on The Last Ship (2014).

He landed his first leading role on the big screen in the German-made feature, Open Water 2: Adrift (2006). He was also a co-star in Marley & Me (2008) and Valentine's Day (2010). In X-Men: The Last Stand (2006) he played the character of Jamie Madrox, the Multiple Man.

On October 29, 2004, in Las Vegas, Eric Dane married actress Rebecca Gayheart. They have two daughters.