Pellington was born in Baltimore, Maryland, the son of Bill Pellington, an All-Pro linebacker who played football with the Baltimore Colts for 12 seasons. Mark graduated from the University of Virginia in 1984, which he attended on an athletic scholarship, playing attack on the lacrosse team. He worked at MTV from 1984–1990, winning awards as a promo producer and creating the landmark TV documentary series Buzz (1990).
He became a freelance director in 1990, directing music videos for U2, Crystal Waters, De la Soul and Pearl Jam. His video for Pearl Jam's "Jeremy" won four MTV awards in 1993, including Best Director and Video of the Year, and his video for Whale's song "Hobo Humpin' Slobo Babe" won the inaugural MTV Europe Music Award for Best Video in 1994.
Pellington then began directing feature films, including Going All the Way (1997), starring Ben Affleck and Rachel Weisz, Arlington Road (1999), starring Tim Robbins and Jeff Bridges, as well as The Mothman Prophecies (2002), starring Richard Gere dealing with mysterious deaths foretold by a strange red-eyed flying creature, Mothman.

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