The river's headwaters are in Santa Rosa and San Jacinto Mountains National Monument.

The river is formed at the west base of the San Jacinto Mountains by the confluence of its North and South forks.

The South Fork flows from near Santa Rosa Summit, through Pine Meadow and Garner Valley to Lake Hemet, which holds 14,000 acre-feet (17,000,000 m3) of water.

Downstream of the dam, the South Fork joins the North Fork east of the town of Valle Vista near Highway 74, and the main stem of the San Jacinto River continues northwest until it discharges into Mystic Lake, a couple of miles east of Lake Perris.

The lake usually has no outflow other than evaporation, but in years of heavy rainfall it overflows into Temescal Creek, which flows northwest to the Santa Ana River in Corona, California.