Born to Charles Lowe and Barbara Hepler in Charlottesville Virginia and raised in Dayton Ohio and Los Angeles, Lowe became famous after appearing in a string of popular movies that included other members of the Brat Pack, the most notable being St. Elmo's Fire.

Lowe and his brother and fellow actor Chad Lowe grew up on the Westside of Los Angeles and attended Santa Monica High School where one of their classmates was fellow Brat-Packer Emilio Estevez. Lowe's sister in law is two time Academy Award winning actress Hilary Swank who is married to Chad, although in May 2006 the couple announced their intention to divorce. Today Lowe makes his home with his wife Sheryl Berkoff and children in Montecito California.

Lowe gained notoriety in 1988 after a video of him having sex with two women, one of whom was underage, became public. He had met the women at a bar, Club Rio, while in Atlanta attending the 1988 Democratic National Convention, and later claimed that he didn't know one of them was underage, and that it was reasonable to assume that someone in a bar was of legal age. The video that was widely circulated was not the one with the underage girl and her lesbian hairdresser girlfriend but that of a threesome with a model called "Jennifer", a young friend called "Justin Morris" and the actor himself, shot in a hotel room in Paris. Lowe was sentenced to twenty hours of community service. He was later committed to a rehabilitation clinic for alcohol and sex addiction.

He is perhaps best known for playing Sam Seaborn in the television show The West Wing, a role which was his from 1999 - 2003. When the show premiered, Lowe's character was to be much more important. But the extremely talented cast � including Allison Janney, Richard Schiff, Stockard Channing, Bradley Whitford, and Martin Sheen (who was only supposed to be a guest star) � soon made the show into the hottest ensemble drama on TV, and Sam Seaborn became possibly the character with the least screen time. Lowe left the show in a highly publicized exit during the fourth season. His exit was quickly followed by that of series creator and writer Aaron Sorkin, and director Thomas Schlamme - a move which saw the show's style change greatly, to mixed reactions from fans.

After leaving, he was star and executive producer of a failed NBC drama, The Lyon's Den (2003). In 2004, he tried again in a series entitled Dr. Vegas, but it also was quickly cancelled.

In 2005 he starred as Lieutenant Daniel Kaffee in a London West End production of Sorkin's play A Few Good Men, the first time the two have worked together since The West Wing. Although Lowe had expressed unhappiness about his role on that show at the time of his departure, he has now repeatedly said that any animosity between them is over and that he was pleased to be working with Sorkin once more, whose talents as a writer he highly regards. Towards the end of The West Wing, Lowe returned to his role of Sam Seaborn, appearing in two of the final four episodes of the show.

Lowe was the first male spokesperson for the 2000 Lee National Denim Day fundraiser which raises millions of dollars for breast cancer research and education. His grandmother and great-grandmother both suffered from breast cancer.

Lowe is a founder of the Homeowner's Defense Fund, a group in Montecito that opposes the building of new housing in California. The organization argues that new housing will degrade existing neighborhoods; the president of the Homeowner's Defense Fund, Sally Jordan, characterized California State advocacy for new housing as `like Hitler'.[1] At the same time Lowe opposes new housing for others, he has sought to build a very large mansion for himself at 700 Picacho Lane in Montecito.[2] Lowe's protest over the appearance of the address in the Santa Barbara News-Press precipitated a mass resignation of senior employees at that newspaper on July 6, 2006.