The game begins with the Master Chief and Cortana awakening from cryosleep on the remains of the UNSC frigate Forward Unto Dawn. They find themselves near a Forerunner planet known as Requiem. As they investigate, they encounter a new enemy faction called the Prometheans, led by the Forerunner warrior known as the Didact.
The plot focuses on the Master Chief's mission to discover the truth behind the Didact's plans and protect humanity from this new threat. At the same time, the game delves into the relationship between the Master Chief and Cortana, as her AI systems begin to deteriorate, a condition known as "rampancy." The emotional bond between the two characters is explored in depth as they face challenges and dangers together.