The Waters of Life: Colonel Autumn is first encountered by the Lone Wanderer during the quest, The Waters of Life, locked in the Project Purity control room at the Jefferson Memorial with James and Janice Kaplinski. He declares the Enclave's intention to confiscate the project, and, in a show of his deadly seriousness, kills Janice in order to force James' cooperation. James, instead of shutting down the project, floods the area with radiation from the purifier, in an attempt to kill Autumn and his men. James and the Enclave soldiers fall to the radiation and die, while Autumn seemingly injects himself with advanced RadAway or Rad-X.
Finding the Garden of Eden: Colonel Autumn is seen again at the end of "Finding the Garden of Eden". He kneels over the Lone Wanderer before the blackout, the latter having been knocked to the floor and stunned by an Enclave pulse-grenade. He orders his troops to secure the G.E.C.K. the Lone Wanderer was carrying.
The American Dream: At Raven Rock, Autumn interrogates the Lone Wanderer, demanding the activation code for the purifier. The code [2-1-6] can be given up (in which case the Colonel will execute the Wanderer with his pistol), lied about, or instead the Lone Wanderer can insult him. In the case of the latter two, Autumn will be interrupted by Eden, who will release the Lone Wanderer. Colonel Autumn later comes on the Raven Rock broadcast system, informing all Enclave troops that the Wanderer is a hostile target and to disregard the President's orders. He then escapes with a group of Vertibirds.
Take it Back!: Autumn is finally confronted by the Lone Wanderer at the end of Take it Back!, just outside the purifier's control room once more. He is accompanied by his two personal bodyguards, a pair of high-level Enclave soldiers equipped with tesla power armor and armed with Gatling lasers or miniguns. Autumn and his men can either be fought, or convinced to leave peacefully through 2 consecutive Speech checks of fairly high difficulty. One speech path involves convincing Autumn to abandon President Eden's insane plans and stop the war; if Raven Rock has been destroyed, another slightly easier Speech path is available in which Autumn can be convinced he has nothing left to fight for and walk away.
During the optional final fight with Autumn, if one of his bodyguards dies, he may pick up their minigun or Gatling laser, which he uses with skill, making him a much tougher foe.
After completing The Waters of Life, Colonel Autumn can be heard on the Enclave Radio informing the people of the Capital Wasteland of the Enclave's mission and warns not to interfere with them.
When faced during the final fight his body may fall down the gap underneath the purifier's control room, making his body unreachable and un-lootable. Killing him is of course optional.
During The Waters of Life quest he may exit the purifier before the door closes, leading to him performing the dialogue looking over his shoulder and being unable to kill Janice, just walking towards the door. This glitch can be solved either by reloading or exiting then entering the room. The latter will cause Autumn to have killed Janice but still be outside the purifier. He will still "die" as normal and can be looted. He cannot be attacked or talked to during this, though an empty dialogue will show up for a short time
"The American people are worth fighting for. The future must be secured. I won't let you stand in the way of that."