At the start of the game, the G-Man speaks to Gordon Freeman in a hallucination-like vision as he pulls Gordon out of stasis and places him on a train going to City 17. When the train arrives, Gordon gets off and proceeds through the Combine's security checkpoints where he is detained by a civil protection officer. Once in an interrogation room, the officer reveals himself to be Freeman's former co-worker and colleague, Barney Calhoun, and helps Freeman to get to Dr. Isaac Kleiner's laboratory.


After meeting Alyx Vance, Freeman is instructed by Kleiner to step into a makeshift teleporter so that he can be safely extracted to the anti-Combine resistance base Black Mesa East along with Alyx, headed by her father, Dr. Eli Vance. However, Kleiner's pet headcrab Lamarr disrupts the machine, and Freeman finds himself — after briefly appearing in several different locations — just outside Kleiner's lab. With the Combine now alerted to his presence, Freeman works his way through the drained canal system,[34] avoiding enemy forces and using the help of human resistance fighters [35] to safely arrive at Black Mesa East.

Dr. Vance and Dr. Judith Mossman debrief Freeman on events since the incident at Black Mesa. As Alyx is introducing Freeman to Dog, her pet robot, and showing him how to use the new Zero-Point Energy Field Manipulator ("gravity gun"), the lab is attacked and Dr. Vance is captured. Freeman is separated from Alyx, but she explains that he must travel to Nova Prospekt, a former prison, in order to save her father.[36] Along the way, Freeman encounters other allies, including Father Grigori in the zombie-infested town of Ravenholm,[37] and Colonel Odessa Cubbage and his forces. After making his way across an Antlion-infested beach, Freeman reaches Nova Prospekt and begins to search for Dr. Vance.[38] Alyx eventually reaches him and joins in his search. Together, they discover that Dr. Mossman is a spy for the Combine, but before they can stop her, she teleports herself and Dr. Vance back to the Combine headquarters known as the Citadel using the Combine teleporter.

Freeman and Alyx follow, and the facility is destroyed by a teleporter malfunction. They materialize in Kleiner's lab one week later, discovering that their actions in Nova Prospekt have inspired the human resistance to mount a full-scale rebellion, turning City 17 into a battlefield.[39] Alyx helps to assist Dr. Kleiner and civilians to escape the city, while Freeman joins with the human resistance to dispatch the Combine forces. As the resistance gains the upper hand, Alyx is captured by the Combine and taken to the Citadel.[40] Freeman enters the Citadel to rescue Alyx. After fighting through many Combine soldiers with only an upgraded Gravity gun, Freeman eventually reaches Dr. Breen's office, where Dr. Mossman is also waiting. As Alyx and Eli Vance are brought in, Dr. Breen attempts to threaten them and convince Freeman to work for him, but Judith Mossman has a change of heart, and releases the three prisoners. Dr. Breen flees to the Dark Energy Reactor at the top of the Citadel and attempts to teleport away from Earth. Freeman pursues him and attacks the reactor.[41] As the reactor explodes a few yards away from Freeman and Alyx, time stops and the G-Man appears. He comments on Gordon's successful endeavors and then places him back into stasis.