Prior to the Raccoon City Destruction Incident, Hunters were being created in large numbers (via the Nursery, or by transportation) to combat the Tyrant in a number of strength tests. However, the Tyrant still hadn't been activated by the time of the Outbreak, and the Hunters escaped.
The Tyrant was activated in the early hours of October 1st by Umbrella scientist Carter to combat the renegade Hunter Rs roaming the facility. Just prior to the escape of the survivors in the lab, the Tyrant revealed its self-awareness, destroying the t-Virus vaccine and knocking both Linda and the detonator for its internal bomb off a catwalk. Without remorse it then killed Carter and proceeded to hunt down the remaining survivors.
After chasing the survivors, David King and Linda, through the ruined city and mutating into a more powerful stage, the Tyrant arrived at the highway overpass and was ready to attack David. Suddenly, Nyx grabbed hold of and absorbed it into its body. Nyx was destroyed by David and it was set free again. Not long after David and Linda flee in an abandoned UBCS truck it then confronted Ada Wong, another fleeing survivor who happened upon the scene while trying to find a way out of the city. She would remark that it was "clever, but predictable" and after a lengthy battle she managed to defeat it and flee. Not long after the battle, his body was destroyed with Raccoon City by missiles.