The player takes the role of an unnamed Hearthian space explorer, referred to as the Hatchling by other Hearthians, preparing for their first space flight as part of Outer Wilds Ventures. They are to be the first explorer to travel with a Nomai text translator tool. Prior to departure, a Nomai statue in a museum activates and turns towards them. The player discovers that whenever the Hatchling dies, a vision of a Nomai mask appears, and they are sent back in time to the start of the game in a time loop. Additionally, the loop resets after 22 minutes regardless, as the sun abruptly goes supernova, destroying the solar system.
The player, through repeated time loops, explores the planetary system and the ruins that the Nomai left behind. From their writings, the Nomai were a nomadic species that explored the universe in large spaceships called Vessels; one Vessel discovered a signal older than the universe emanating from the Hatchling's star system. Upon warping to the system, the Vessel became embedded in Dark Bramble, with some of the Nomai surviving in escape pods. No longer able to detect the signal, the Nomai built a civilization throughout the system while trying to find the source, dubbed the "Eye of the Universe". They eventually discover that, with enough power, they can send objects or information backwards in time using a linked pair of black and white holes. This inspires them to build a probe cannon in orbit around Giant's Deep to fire a probe in a random direction to locate the Eye, and a station in orbit around the star, the Sun Station, that would artificially induce a supernova, generating enough power to send the probe's data back in time 22 minutes. Together, this would allow the probe to be fired in as many times and directions as necessary to find the Eye, at which point the Nomai would shut down the Sun Station, ending the time loop. However, the Sun Station failed to induce a supernova and before an alternate power source could be found, the Interloper entered the solar system. The Nomai investigating found that the Interloper contained an extremely pressurized source of "ghost matter", a highly lethal and invisible substance. Before they could inform the others, the source ruptured and a powerful wave of ghost matter spread throughout the system, killing all of the Nomai.
A long time later, after the animals of Timber Hearth evolved into the Hearthians, the sun goes supernova as part of the natural end of the universe, triggering the time loop repeatedly until the probe cannon finds the Eye at the beginning of the game and through the statue inducts the Hatchling into the loop. Armed with this knowledge, the Hatchling is able to repower the Vessel and warp to the Eye. Upon entering the Eye, the Hatchling encounters echoes of the other members of Outer Wilds, as well as a Nomai if they had met on the Quantum Moon. As the universe ends the Eye creates a new universe in a Big Bang. The ending shows a similar planetary system with new life forms 14.3 billion years after its creation, with influences of the Hearthians and Nomai.