Lowe was born in Charlottesville, Virginia, to Barbara Lynn (née Hepler), a schoolteacher and native of Connecticut, and Charles Davis Lowe, a trial lawyer. His parents divorced when Lowe and his younger brother Chad were young. Lowe was baptized into the Episcopal church. He is of German, English, Irish, Scottish and Welsh ancestry. On the show Who Do You Think You Are?, Lowe found out that one of his ancestors, Christopher East, was a Hessian soldier. His ancestor was fighting under the command of Colonel Johann Gottlieb Rall and was captured at the American victory at Trenton, New Jersey, on the morning of December 26, 1776. As an American POW, his ancestor was given a choice, and took the option to stay in the United States. Lowe was raised in a "traditional American setting" in Dayton, Ohio, attending Oakwood Junior High School, before moving to the Point Dume area of Malibu, California, with his mother and brother. In California, he attended Santa Monica High School, where he met Charlie Sheen. In his autobiography Stories I Only Tell My Friends, he wrote regarding Sheen, "We were both nerds [...] he wanted to be a baseball player."
He spent the 1980s as a member of the "Brat Pack", a group of young, powerful and reckless actors and actresses that included Emilio Estevez, Charlie Sheen and Judd Nelson, among others. In 1988 Lowe was involved in a scandal centering around a sexually explicit videotape which involved a minor, for which he did 20 hours of community service in Dayton. He subsequently sought help for his problems with drugs and alcohol and has re-emerged in the 1990s as a clean and sober husband and father.
In July 2010, it was announced that Lowe would be providing the voice for the superhero Captain Marvel in the upcoming animated series, Young Justice. It was also announced in July 2010 that Lowe would become a series regular on the series Parks and Recreation. In late autumn 2017, Lowe began a reality series with his two sons, 24-year-old Matthew and 22-year-old Jon Owen, on A&E titled The Lowe Files. With the exception of the hour-long pilot, the series features 30-minute road trips with the Lowe boys, and occasional TV guest stars known in the field, investigating common urban myths and legends that Rob has loved since he was a young boy and has shared with his boys throughout their growth, sometimes to the frustration of the boys' mom and Lowe's wife, Sheryl. Some of the topics being explored are Bigfoot/Sasquatch, the alleged unidentified "submerged" objects that may have a base off the coast from Los Angeles, alien abduction, and ghosts and their direct responses to stumuli. The series debuted on August 2, 2017. In October 2018, it was announced that Lowe will star in a new ITV series, Wild Bill, about an American policeman who moves to Boston, Lincolnshire with his daughter. On March 19, 2019, Lowe began hosting the Fox competition series Mental Samurai where he also serves as a producer.
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