Lowe had recurring roles on Melrose Place, Popular, Now and Again, and ER, and guest-starring roles on Touched by an Angel, Superman, CSI: Miami and Medium. Lowe's feature film appearances have included roles in Nobody's Perfect, True Blood, Quiet Days in Hollywood, Floating, and Unfaithful. In 2000 he portrayed iconic singer John Denver in the made-for-television movie Take Me Home. That year he also wrote and directed the short film The Audition. Lowe made his feature film directorial debut in 2007 with Beautiful Ohio. Lowe has directed episodes of Bones, Brothers and Sisters, Law & Order: Special Victims Unit, Hack, Without a Trace, and Pretty Little Liars.