Captain Jacob Keyes, having spent 35 years in the military, was known for being a great strategist and leader. During the time of Halo: Combat Evolved, Keyes was escaping Reach with Master Chief aboard the Pillar of Autumn. Cortana sent them to Halo Installation 04 using some ambiguous coordinates she found on a Forerunner artifact, but the Covenant caught up with them within a few minutes. After Master Chief escapes with Cortana, Captain Keyes steered the Pillar of Autumn into the Halo, and survived. Soon afterwards he was captured and brought aboard The Truth and Reconciliation, a Covenant ship. Master Chief is sent to rescue him. After heading back to Alpha Base, Keyes found what he thought was a weapon cache, but it turned out to be a Flood facility and he was captured by the Flood.

The Flood turned him into a Combat Form, but they later realized he was of importance. They then changed him into a Brain Form in an attempt to get information out of him. He managed to hold them off long enough for Master Chief to kill him and get his Command Neural Interface. His corpse was destroyed with Halo's destruction.

His daughter Miranda Keyes lived on, and became increasingly involved with the story of the Halos and the war with the Covenant.