McComb started acting at age two in a commercial for Publisher’s Clearing House. In 1989 she played the titular character in the Francis Ford Coppola-directed segment “Life Without Zoë”, from the anthology film New York Stories. She was on the 1990 television program The Outsiders playing the part of Scout. The show only lasted 1 season. When she appeared in the telefilm Generation X in 1996, she became the first actress to portray the X-Men character of Jubilee on screen. In 1997, McComb started the television series Profiler as Frances Malone. The next year she joined the cast of Party of Five, playing the part of Maggie.
On July 5, 2003, McComb married actor James Van Der Beek. They separated in April 2009, and on November 20, 2009, Van Der Beek filed for divorce. The divorce was finalized on March 31, 2010 and enforced on June 3, 2010.