McGowan, the second oldest of six children (including two half-siblings), was born in Florence, Italy to Daniel McGowan (an Irish-born artist) and Terri (a French American writer); her parents were members of the Children of God and her father ran the Italian chapter of the group. McGowan spent her early childhood in the group's communes and travelling Europe with her parents. Through her father's art contracts, Rose had become a child model and had appeared in Vogue Bambini and various other Italian magazines. Her parents divorced when Rose was ten. She subsequently lived in Oregon and Gig Harbor, Washington. McGowan did not speak English until she moved to the U.S.

McGowan's high school years were spent with her father in Seattle attending Roosevelt High School. At the age of fifteen, McGowan officially emancipated herself from her parents. Rose pursued a possible career in the film industry during her late teens. She also enrolled in a beauty school as a back-up.

McGowan's first attempt to "break" into Hollywood came in the form of a bit-role in the 1992 Pauly Shore comedy Encino Man. Her role in the 1995 black comedy, The Doom Generation, brought her to the attention of film critics and she received a nomination for "Best Debut Performance" at the 1996 Independent Spirit Awards. She was subsequently cast as Tatum Riley, the best friend of Neve Campbell's character Sidney, in the 1996 hit horror-satire film, Scream.

McGowan spent the majority of the 1990s appearing in low-budget films, including parts in Southie, Going All the Way and Lewis & Clark & George. She appeared opposite Peter O'Toole in the 1998 movie adaptation of Phantoms, based on a novel by Dean Koontz. Notably, she also starred in the 1999 black comedy, Jawbreaker, where she played a high school student who tries to cover up a classmate's murder. The role of Courtney Shayne earned Rose a nomination for Best Villain at the 1999 MTV Movie Awards.

In 2001, after some forgettable roles (including a small role in the wrestling-themed movie Ready to Rumble, which performed poorly at the box-office), McGowan was cast as Paige Matthews in the popular television series Charmed, as a replacement lead actress after Shannen Doherty's resignation from the show. Rose was offered to be a producer after the seventh season, but turned it down. The series ended its run in May 2006.

In May 2005, she portrayed actress/singer Ann-Margret in Elvis, a CBS mini-series about the life of Elvis Presley. That same year, Rose lent her voice to the video game Darkwatch as a femme fatale named Tala. The game was published by Capcom for PlayStation 2 and Xbox.

McGowan can be seen starring in the upcoming Quentin Tarantino/Robert Rodriguez double-feature Grind House, scheduled to be released on April 6, 2007. She also will have a brief appearence in the upcoming Brian de Palma film The Black Dahlia.

McGowan was the face of American clothing company bebe from 1998-1999. She was also the cover model for the Henry Mancini tribute album Shots in the Dark, which was released in 1996.

In addition to clothing endorsements, McGowan has appeared on numerous magazine covers including Seventeen, Interview, Maxim and GQ. Rose has also been featured on Maxim, FHM and Stuff magazine's sexiest women lists.

McGowan gained a reputation for playing brassy, violent characters. Especially in the film Devil In The Flesh where she played a serial murderer and stalker while still in high school. In one especially violent scene, she sent her grandmother to a bloody death with her own cane. She was in a very public five-year relationship with shock-rocker Marilyn Manson, and often appeared with him at celebrity events in extremely provocative clothing, such as the chain mail transparent dress and thong she wore to the 1998 MTV Video Music Awards. McGowan later ended their two-year engagement over "lifestyle differences." She has since gone on to have relationships with fellow actor Kip Pardue, TV personality Ahmet Zappa and Men's Health magazine editor David Zinczenko.

McGowan used to live in Seattle but currently lives in Los Angeles. At one point, she suffered from obsessive compulsive disorder. As a victim of sexual assault, McGowan has led discussions on the subject among campus groups.

McGowan is an avid lover and activist for Boston Terriers. She has two herself, Bug and Fester, and has personally donated to various Boston rescues. She 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."

While dating Marilyn Manson, she appeared in a music video for the song Coma White, and also performed backing vocals on the song Posthuman. Both these songs are available on the album Mechanical Animals. Rose appeared on a BT track called Superfabulous from his album Emotional Technology. The song has gone on to be featured in films including Win a Date with Tad Hamilton and Raising Helen. She has written and recorded a song titled "Protection" which was featured in her 2001 film Strange Hearts.

Rose has also appeared in the Imperial Teen music video for Yoo Hoo, which was featured on the Jawbreaker soundtrack.

In the Charmed epsiode "Sense and Sense Ability," Rose performed, in character, a cover of the Peggy Lee classic Fever.

McGowan has expressed interest in recording an album of her own. During an interview with Living TV she has stated: