He is a high school graduate of the Las Vegas Academy of International Studies, Performing and Visual Arts, where he majored in acting, because the school didn't offer his first love, filmmaking. He is a college graduate of New York University's Tisch School of the Arts where he majored in film directing. Gubler's parents were both born in Las Vegas and his Mother, Marilyn Gubler, was the first woman to serve as Republican state Chairman. His Grandfather Maxwell Kelch was the first president of the Las Vegas Chamber of Commerce and founded Las Vegas' first radio station (KENO). Gubler's sister Laura Dahl is an accomplished fashion designer who is based in New York city.

Gubler reluctantly worked as a model to put himself through film school, working with DNA Model Management, Tommy Hilfiger, and numerous fashion designers. Gubler was interning for Wes Anderson at the same time he was modeling, and Anderson encouraged him to audition for a part in his movie "The Life Aquatic". Gubler did, and landed the role of Intern #1. This led to his role as Dr. Spencer Reid in Criminal Minds. He had a small role in the 2006 film RV as the disreputed Joe Joe and voiced the character of Simon in 2007's Alvin and the Chipmunks, alongside Jason Lee, Jesse McCartney and Justin Long.

While making The Life Aquatic with Steve Zissou, Gubler made the documentary entitled Matthew Gray Gubler's Life Aquatic Intern Journal, a behind the scenes view of the making of the film, which was later included in some DVD releases. Gubler has directed and starred in a series of self-deprecating mockumentaries called Matthew Gray Gubler: the Unauthorized Documentary in which he parodies Hollywood behavior, which are filmed while onset of Criminal Minds. He directed, edited, and co-produced the music video for "Don't Shoot Me Santa" by the rock band The Killers.

• The Life Aquatic With Steve Zissou (2004) .... Intern #1 (Nico)
• Criminal Minds (2005-) TV Series .... Dr. Spencer Reid
• RV (2006) .... Joe Joe
• Alvin and the Chipmunks (2007) .... Simon Seville (voice)
• The Great Buck Howard (2008)
• Pornstar (2008) (completed) .... Ziggy
• How to Be a Serial Killer (2008) (completed) .... Bart
• 500 Days of Summer (2008) (post-production)
• Alvin and the Chipmunks: The Squeakuel (2009) .... Simon Seville (voice)
• Rapunzel (2010) (filming) .... Young Prince (voice)

• Claude: A Symphony of Horror (2001)
• Dead or Retarded (2001)
• The Cactus That Looked Just Like a Man (2004) (Also writer, cinematographer, producer and editor)
• Matthew Gray Gubler's Life Aquatic Intern Journal (2005) (Also writer, cinematographer, producer and editor)
• Whirlwind Heat's music video for Reagan (2006)
• The Killers' music video for "Don't Shoot Me Santa" (2007)
• Matthew Gray Gubler:The Unauthorized Documentary Episode 1
• Matthew Gray Gubler:The Unauthorized Documentary Episode 2
• Matthew Gray Gubler:The Unauthorized Documentary Episode 3
• Matthew Gray Gubler:The Unauthorized Documentary Episode 4
• Matthew Gray Gubler:The Unauthorized Documentary Episode 5
• Matthew Gray Gubler:The AUTHORIZED Documentary Episode 1