Black Mesa Research Facility is an ultra-secret laboratory under government contract, conducting top-secret and extremely volatile experiments. The scientist Gordon Freeman a Black Mesa employee. This morning, as usual, he pits his way to the research facility for a run-of-the-mill experiment. However, when the experiment initiates, Gordon realizes that it might not be as ordinary as he thought. Odd things begin to happen as he makes his way to one of the Black Mesa test chambers. Even weirder things happen when he starts to move the test sample towards the antimass-spectrometer.

At that moment everything goes horribly wrong. Aliens from the planet Xen have suddenly invaded the facility, injuring or killing many of the employees. The Marines have come to the facility to kill off the aliens and the surviving witnesses of the accident. Gordon understands what that means: he will have to fight his way through aliens and Marines to get to the top of the Black Mesa complex and much beyond.

The story of Half-Life is told entirely in-game: everything is seen through the eyes of the protagonist. Most story elements unfold via scripted sequences, triggered by the player reaching a certain area. If other characters have information to reveal, they address the player directly. The Black Mesa complex in the game is not made up of distinct levels, but is mostly a continuous world, where it is possible to backtrack through large parts of the game.

The game's weapon arsenal is, to a large part, made up of realistic weapons like pistols, machine guns and explosives, but there are also futuristic energy weapons developed at Black Mesa as well as organic weapons acquired from the invading aliens. Most weapons feature an alternate firing mode.

Enemies fall into two categories: aliens and human soldiers. While most of the aliens are not very bright, the humans display some relatively advanced artificial intelligence: they seek cover, retreat when hit and try to drive the player from his cover by throwing grenades. Some of the alien enemies can not be killed by normal means. The environment must be used against them instead, going with a general tendency of the game to alternate the combat with environmental puzzles.