Pink salmon in their native range have a strict two year life cycle, thus odd- and even-year populations do not interbreed. Adult pink salmon enter spawning streams from the ocean, usually returning to the water course, or race, where they originated. Spawning occurs between late June and mid-October.

Pink salmon spawn in coastal streams and some longer rivers, and may spawn in the intertidal zone or at the mouth of streams if hyporheic freshwater is available. Using her tail, the female digs a trough-shaped nest, called a redd, in the gravel of the stream bed, wherein she deposits her eggs. As she expresses the eggs, she is approached by one or more males who fertilize them as they fall into the redd.

Subsequently, the female covers the newly-deposited zygotes, again with thrusts of her tail against the gravel at the top of the redd. The female lays from 1000 to 2000 eggs in several clutches within the redd, often fertilized by different males. Females guard their redds until death, which comes within days of spawning. In dense populations, a major source of mortality for embryos is superposition of redds by later-spawning fish. The eggs hatch from December to February, depending on water temperature, and the juveniles emerge from the gravel during March and April and quickly migrate downstream to estuaries at about one-quarter gram. The fish achieve sexual maturity in their second year of life. They return to freshwater in the summer or autumn as two year old adults. Pink and chum salmon sometimes interbreed in nature to form the hybrid known as the miko salmon; the hybrids are reproductively sterile.

Pink salmon were introduced into the Great Lakes; this is the only location where they have been successfully introduced into an entirely fresh water environment. In the Great Lakes, they are most common in Lake Superior but are rare in Lake Michigan.