Cretton was born in 1978 in Haiku, Hawaii on the island of Maui. He is of half-Japanese descent. He was home-schooled by his Christian mother. His sister Joy is a costume designer who has worked on several of Destin's projects. He lived in Haiku in a two-bedroom house with his five siblings, until he was 19 years old. He moved to San Diego, California to attend Point Loma Nazarene University, where he majored in communications. After graduating, Cretton worked for two years as a staff person at a group home for at-risk teenagers.
He made short films as a hobby, which developed as a vocational path. He attended and graduated from film school at San Diego State University.

While at San Diego State University, Cretton made a 22-minute short film, Short Term 12, based on his experiences at the facility for teenagers. The short film premiered at the 2009 Sundance Film Festival, where it won the Jury Prize in Short Filmmaking.

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