The Resistance was formed shortly after the Seven Hour War in response to the Combine takeover. A loose band of guerillas, outlaws and spies dedicated to overthrowing the new world order, they were unable to take on the alien empire directly. So the Resistance instead worked at undermining it by infiltrating the ranks of Civil Protection, smuggling weaponry, setting up a sophisticated underground with bases at Ravenholm, Black Mesa East and White Forest, and by helping civilians escape the Combine controlled cities.

Many of the Resistance's key members are Black Mesa personnel who survived the Black Mesa Incident and the events that took place afterward. Other key members seem to have become leaders due to useful knowledge or experience.

From its formation until the Combine War, the Resistance mostly operated underground, with safehouses, hidden bases and concealed supply caches in and around City 18. One of the few exceptions to this appears to have been The Coast, where the Resistance had sufficient strength to operate more openly, with a number bases and outposts, including Shorepoint, New Little Odessa, Bridge Point and Lighthouse Point. Operating from these positions, they regularly sparred with the Combine forces in the area. Over time, though, the Combine made significant inroads into the Coast, destroying many of the smaller outposts and condensing the spread out Resistance forces into larger groups at the main bases. Bridge Point was taken over and occupied, possibly due to the significance of the railway bridge beside it, which the Combine Razor Trains use.