It's 2418, and the Planetary Union promotes Ed Mercer to Captain of the exploratory vessel The U.S.S. Orville. Ed's enthusiasm for his new position is dampened when his ex-wife, Kelly Grayson, is assigned to be his First Officer. While on their first routine mission, the Orville crew is ambushed by the Krill, a vicious alien race, who are bent on stealing a device that can cause time to accelerate.

The Orville crew is divided between cultures when Bortus and Klyden debate if their newly born offspring should receive a controversial surgery.