The series follows the voyages of the Starfleet starship USS Enterprise (NCC-1701), captained by Christopher Pike, during its second five-year mission (2259-2264), which precedes Captain James T. Kirk's five-year mission narrated in the television series Star Trek. The series picks up on stardate 1738.12 (2259), a couple of years after the events that occurred in the second season of the television series Star Trek: Discovery, when Pike temporarily captained the USS Discovery.

In season two, the crew of the U.S.S. Enterprise, under the command of Captain Christopher Pike, confronts increasingly dangerous stakes, explores uncharted territories and encounters new life and civilizations. The crew will also embark on personal journeys that will continue to test their resolve and redefine their destinies. Facing friends and enemies both new and familiar, their adventures will unfold in surprising ways never seen before.