It's 2417, 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.

Ed and the Orville crew encounter a massive vessel adrift in space, which is in danger of colliding with a star. While some of the crew set out to help the ship's inhabitants, Bortus, Gordon, and John stay behind and fend off a Krill attack on another Union ship

After the crew saves a stranded ship and its attractive captain, Ed becomes smitten with the Orville’s new guest, while Kelly suspects all is not what it seems. Meanwhile, Gordon attempts to teach Isaac the art of pulling off a practical joke.

After the Orville crew defeats a Krill attack on a brand-new colony, the Union sends Ed and Gordon on a dangerous undercover mission to infiltrate a Krill ship and obtain a copy of the Krill bible, the "Anhkana," to better understand the enemy.

When two Union anthropologists go missing on a planet similar to 21st century Earth, Ed sends a team led by Kelly to find them, but the mission quickly goes awry when they realize the society’s government is completely based on a public voting system to determine punishment.

Ed and the crew set out to save Dr. Finn, her two sons and Isaac after their shuttle gets thrown into uncharted space and they crash-land on a moon that is light years from the Orville.

The Orville is called to mediate a peace treaty between two warring cultures, but tensions run even higher between Ed and Kelly when a familiar face boards the ship. Meanwhile Yaphit declares his love for Dr. Finn with surprising results.

When a fire breaks out on The Orville and a crew member dies, Alara begins to question if she is fit for her job, just as unusual and terrifying things start happening on the ship.

Kelly discovers that Lt. John Lamarr is smarter than he lets on. So, she pushes Ed to consider him for a key leadership position on the ship after The Orville gets damaged by a mysterious spatial anomaly causing harrowing effects to all things living.

Ed and Kelly consider the possibility of reforging their relationship, but Kelly soon crash-lands on a planet in another universe with Isaac and Gordon.