Witwer grew up in Glenview, Illinois, a small suburb outside of Chicago.
He attended Glenbrook South High School, during which time he was involved in drama and theater classes, as well as being the lead singer of a high school band called "Love Plumber".
He attended the Juilliard School for a time before moving to Los Angeles.
From there, he became the complete basis for the main character's voice and appearance in Star Wars: The Force Unleashed.
His likeness was created through motion capture for the game to build the character's appearance and range of facial expressions.
From 2011 to 2014, Witwer portrayed the lead vampire Aidan in the Syfy Channel's remake of the BBC original series Being Human. Hyde from the sixth season in the ABC series Once Upon a Time.
When Amy Beth Christenson's original concept art of Galen Marek looked strikingly like Sam Witwer, the vice president at the time noted the resemblance due to recognizing Witwer for Battlestar Galactica so he was contacted to audition.
During the live show "Behind the Force", Sam showed his acting skills by saying one or two lines of the characters that he's played in the Star Wars universe.
Sam also guest voiced an alien as well as a stormtrooper during the siege of Maz Kanata's palace in Star Wars: The Force Awakens.Although uncredited, he also portrayed Major Zod in the last scene of the Season eight finale while the character would be portrayed by British actor Callum Blue for the duration of the show's ninth season.In 2010 he starred as a walker in the pilot episode of AMC's The Walking Dead.There, he attended Glenbrook South High School and became involved in theater as well as becoming the lead singer in a band called "Love Plumber".After receiving marks that were less than satisfactory, Witwer later attended the Juilliard School for drama stating that it was the only school that accepted him on the fact that they didn't look at his transcripts.He has since received much praise for his contribution to the role.