He is known for his work in the horror genre, directing films such as The Exorcism of Emily Rose (2005), Sinister (2012), and The Black Phone (2021).

[4] Derrickson co-wrote and directed The Exorcism of Emily Rose, which was loosely based on a true story about Anneliese Michel.

Derrickson next directed a remake of The Day the Earth Stood Still, starring Keanu Reeves and Jennifer Connelly, written by David Scarpa.

[7] In August 2011, Derrickson teamed up with producer Jason Blum to write and direct Sinister, a mystery-horror film starring Ethan Hawke.

[8] The $3 million picture was released in theaters by Summit Entertainment on October 12, 2012, and received generally positive critical reviews.

[9] Deliver Us from Evil (2014) was produced by Jerry Bruckheimer,[10] and is based on a 2001 non-fiction book entitled Beware the Night by former police Sergeant Ralph Sarchie and Lisa Collier Cool; its marketing campaign highlighted that it was "inspired by actual accounts".

[13] In January 2020, Derrickson announced that he had stepped away from directing duties as a result of unspecified creative differences, after which Sam Raimi took over.

[15] In 2021, Derrickson directed an adaptation of Joe Hill's short story "The Black Phone", from a script he co-wrote with C. Robert Cargill.

[16] Produced by Blumhouse Productions and Universal Pictures, The Black Phone re-teamed Derrickson with Ethan Hawke and James Ransone, and was theatrically released to positive reviews on June 24, 2022.