

McGowan, the second-eldest of six children (plus two half-siblings), was born in Florence, Italy, the daughter of Terri, an American writer of French descent, and Daniel McGowan, an artist of Irish descent. Daniel McGowan ran an Italian chapter of the Children of God to which both he and his wife held membership until 1978. McGowan spent her early childhood amid the group's communes, often traveling Europe with her parents. Through her father's art contacts in Italy, McGowan became a child model and appeared in Vogue Bambini and various other Italian magazines. Her parents returned to the United States when she was 10, when they divorced. She subsequently relocated to Oregon and then to Gig Harbor, Washington, where she also met childhood friend Rey-Phillip Santos. McGowan did not speak English until she moved to the U.S.
McGowan's formative years were spent with her father in Seattle, Washington, attending Roosevelt High School and Nova Alternative High School. At the age of 15, she officially emancipated herself from her parents. McGowan pursued a possible career in the film industry during her late teens, and also enrolled in a beauty school as a back-up.

McGowan lived in Seattle, Washington, but currently resides in Los Angeles, California. She was in a very public 3 ½-year relationship with rock musician Marilyn Manson. After a formal engagement lasting two years, McGowan ended the relationship over "lifestyle differences". Prior to the release of Grindhouse, there was speculation that McGowan was dating director Robert Rodriguez. In May 2007, it was reported that they confirmed their relationship while appearing hand-in-hand at the Cannes Film Festival. On October 12, 2007 it was announced by Zap2it.com that McGowan was engaged to Rodriguez. They planned to wed in 2009, but reportedly split on October 2, 2009.
McGowan has admitted to sleepwalking as a child. "The weirdest spot I ever woke up was a snow bank in Montreal. Now I just speak Italian in my sleep." McGowan also suffers from agoraphobia, an anxiety disorder.
McGowan is known as an activist for Boston Terriers. She herself has two, Bug and Fester, and has personally donated to various Boston rescues. McGowan reportedly encouraged friends to donate to Boston Terrier Rescue Net, and according to BTRN: "Having fallen in love with Bug and Fester, her friends donated generously. It amounted to a considerable contribution, which will go a long way in helping BTRN and the needy volunteers who selflessly give to deserving Bostons."
According to an article in the New York Post, McGowan suffered serious injuries in a car accident early in 2007. Riding as a passenger, her car was struck by another vehicle and the force of the impact drove her eyeglasses into her face. McGowan is quoted as saying, "I didn't realize I was hurt until I put my hand to my face and felt the flap of skin. My glasses had sliced me under my eye." After obtaining the services of a plastic surgeon, McGowan is reported to be suffering no long-lasting consequences from the incident.
Of her acting method, McGowan said "I'm not really one of those people who goes and writes some big backstory and agonizes over characters...For me personally, it's just kind of more instinctive. But I don't have kind of an acting background. I fell into it accidentally."

McGowan, whose paternal family originates from County Cork, has expressed support for the cause of the Irish Republican Army (IRA), with the reports of her comments being released into the media on September 11, 2008. After starring in Fifty Dead Men Walking, she was quoted as saying "I imagine had I grown up in Belfast, I would 100% have been in the IRA. My heart just broke for the cause. Violence is not to be played out daily and provide an answer to problems, but I understand it." Her comments were attacked by the author of the autobiography upon which the film is based, Martin McGartland, who said "Rose McGowan's comments were insulting to victims of IRA terrorism and she should apologize."