Fessenden has operated the production company Glass Eye Pix since 1985. Fessenden was influenced by the old Universal Monsters.
An actor, screenwriter, director and film editor, he has worked, in addition to feature films, on such television projects as the NBC horror anthology Fear Itself (2008), directing the episode "Skin and Bones". He wrote the screenplay of Orphanage (2007) with Guillermo del Toro, an English-language remake of El Orfanato.
Fessenden has worked as a mentor to young directors, such as Jim Mickle and Ti West. He has been a producer on projects including Ilya Chaiken's Liberty Kid (2007), Kelly Reichardt's Wendy and Lucy (2008), James McKenney's Satan Hates You (2010), West's The House of the Devil (2009) and The Innkeepers (2011), Joe Maggio's The Last Rites of Joe May (2011), and Rick Alverson's The Comedy (2012). Under his low-budget horror banner ScareFlix, Fessenden has produced films including West's The Roost (2005) and Trigger Man (2007), Glenn McQuaid's I Sell the Dead (2008), Maggio's Bitter Feast (2010), and Mickle's Stake Land (2010).
As a character actor, Fessenden has appeared in numerous films, including Martin Scorsese's Bringing Out the Dead (1999), Steve Buscemi's Animal Factory (2000), Brad Anderson's Session 9 (2001) and Vanishing on 7th Street (2010), Jim Jarmusch's Broken Flowers (2005), Neil Jordan's The Brave One (2007), McQuaid's I Sell the Dead (2008), Reichardt's Wendy and Lucy (2008), Mickle's Mulberry Street (2006) and Stake Land (2010), and Joe Swanberg's Silver Bullets (2011). Fessenden stars in and has directed the films Habit (1997), Wendigo (2001), and The Last Winter (2006). Fessenden also starred in the Sundance Film Festival pictures River of Grass (1994) directed by Reichardt, and Margarita Happy Hour (2001) directed by Chaiken.