The Anza expedition camped by the river on March 30, 1776, and named it the Río de Nuestra Señora de Guadalupe. The pueblo and the first Mission Santa Clara were founded near its banks in 1777, and both moved away to escape its floods. Its mainstem runs about 14 miles from Almaden through downtown, where Los Gatos Creek joins it, to the Bay at Alviso Slough. The Muwekma Ohlone name for it is Thámien Rúmmey.
Steelhead and Chinook salmon still run up the river, making San Jose the southernmost major U.S. city with known salmon spawning runs. In 2005 a local resident, Roger Castillo, found the bones of a young Columbian mammoth in the riverbank; nicknamed Lupe, the fossils are shown at the Children’s Discovery Museum. Downtown, the 120-acre Guadalupe River Park and its trail follow the river for about 2.6 miles.