As a Screenwriter, Spaihts became known in the film industry as a "go-to guy for space thrillers", when his science fiction romance Passengers was included on the 2007 Black List of unproduced high-value screenplays. Keanu Reeves and Stephen Hamel had hired Spaihts to write the film after originally becoming attached to Spaihts' abandoned science fiction script Shadow 19. After Reeves agreed to produce with Hamel and star in Passengers, Spaihts was commissioned by Scott Free to write the next installments in the Alien saga, two prequel films to be directed by Ridley Scott, which eventually turned into the more autonomous story Prometheus, ultimately revised by Damon Lindelof. For New Regency Spaihts also wrote the screenplay to the alien invasion thriller The Darkest Hour, based on a story by Leslie Bohem and M.T. Ahern.

Spaihts has worked on a film version of St. George and the Dragon for Sony Pictures, and originated a Disney film project called Children of Mars. In 2012 he entered a two-picture deal at Jerry Bruckheimer Films to adapt Ashley Wood's graphic novel World War Robot and write a space adventure film based on his own original pitch.

In 2013, Spaihts began work on the story for the Black Hole remake by Walt Disney Studios. The rights to his early science fiction screenplay had originally been sold to the Weinstein Company, with Keanu Reeves and Reese Witherspoon set to star, and Game of Thrones Director Brian Kirk at the helm. The project was later made into the 2016 film Passengers by Sony Pictures, produced by Original Film and Company Films, directed by Morten Tyldum, and starring Jennifer Lawrence and Chris Pratt.

He co-wrote the script for Marvel Studios' 2016 live action Doctor Strange film. Spaihts also co-wrote the reboot of The Mummy franchise for Universal, directed by Alex Kurtzman.