New York City, Earth, 2018. Ed Mercer, an officer with the Planetary Union, finds his wife in bed with a blue (literally BLUE) lover and ends their marriage by walking out.
A year later, despite poor evaluation reports for drunken and slovenly behavior in the wake of his divorce, he is offered the command of the U.S.S. Orville, a mid-level exploratory vessel.
Needing a helmsman, Mercer brings his best friend, Gordon Malloy on board despite the Admiral's misgivings. He tracks Gordon down on a recreational holographic deck where he's battling a samurai ogre named Justin.
Mercer meets his crew and has a short face-to-face meeting with his new senior staff which include: Alara Kitan, a very young, very strong Xelayan woman; Lt. John LaMarr, a human navigator who likes his soda privileges; Lt. Commander Bortus, a Moclan, a species with a single gender who only urinate once a year; Dr. Claire Finn, an amazing medical officer who seeks to be where she is most needed; and the Science and Engineering officer, Isaac, a representative of the purely mechanical Kaylon society which views all biological species as inferior.
LaMarr and Malloy suss each other out and establish a casual rapport.
Mercer takes his first mission from the Admiral, a supply run to a science station on Epsilon-2.
En route, the bridge crew discuss their destination and establish that it is a first-rate scientific facility with no bars and no strip joints. Kitan conveys a message to Mercer that a First Officer has been found for the Orville. Seeing the officer's profile, Mercer immediately runs to his office (accidentally trampling Yamphit, a gelatinous creature voiced by Norm MacDonald) to speak to the Admiral via visual com because the officer selected is his ex-wife, Kelly Grayson.
Mercer and Grayson have a tense re-introduction involving some apologies on Grayson's part but mostly blame on both sides which the entire bridge crew can apparently hear through the walls.
Grayson and Malloy bump into each other in the corridor and have an awkward chat.
Arriving at Epsilon-2, they discover the supplies they have brought are not needed, that the request for a Union starship was covering a major secret scientific breakthrough that can accelerate time within a contained field. Dr. Aronov needed to keep the device a secret from the enemy Krill species. During their tour, he shows them a seed that can grow a redwood in any environment.
When Mercer contacts the Orville to begin transport of the device, one of the technicians turns a weapon on them and reveals himself to be a Krill agent, killing the scientist who created the device by knocking her into the accelerated time bubble.
Kitan manages to disarm and subdue Derek but the Krill have arrived and the away team has to fight their way out. Meanwhile, the Orville crew are working hard to evade and fight the Krill vessel.
The away team make it to the shuttle but have been boarded by a single Krill soldier. Mercer makes a sudden stop with the shuttle, knocking the un-seatbelted enemy out when he falls off-balance.
Reaching the Orville, they realize the ship is disabled and the Krill have them at their mercy. After playing for some time by roping the Krill captain into a discussion on healthy marriages, they come up with a plan, rigging the device with a glue gun and a red wood seed to destroy the Krill vessel when it is activated.
While the ship is being repaired, Grayson offers to transfer to another ship but Mercer asks her to stay. Grayson meets with the Admiral and it's revealed that she was the reason that Mercer got the Orville command in the first place.