Romijn (pronounced "Ro-mane") was born in Berkeley, California, to Jaap Romijn and Elizabeth Kuizenga, both of whom are of Dutch ancestry. Her friends nicknamed her "the jolly blonde giant" because her height is just under 6 feet.

While studying music (voice) at the University of California, Santa Cruz, she became involved with modeling and eventually moved to Paris, France for more than two years. Among other jobs, Romijn modeled for the swimsuit issue of Sports Illustrated and for Victoria's Secret. She also was the host of MTV's House of Style from 1998 to 2000. Romijn is fluent in French and Portuguese.

In 2000's X-Men, Romijn had her first major movie role as "Mystique"; she returned to the role in 2003's sequel X2: X-Men United, and again for X-Men: The Last Stand (2006). In these movies her costume consisted of blue makeup and some strategically placed prosthetics on her otherwise nude body. In X2: X-Men United she shows up in a bar in one scene in her "normal" look, and also in X-Men: The Last Stand.

She had her first leading role in Brian De Palma's Femme Fatale (2002). She also has starred in movies such as Rollerball, The Punisher and Godsend.

She played the leading role in Pepper Dennis, a TV series on The WB. This series showcased Romijn's talents for comedy, singing, modeling, drama, and adventure.

She married actor John Stamos on September 19, 1998. During her marriage, she used the name Rebecca Romijn-Stamos in both her personal and professional life. The couple announced their separation on April 12, 2004 and divorced on March 1, 2005.