[5] Santa Ysabel Creek rises in the northeastern corner of the San Dieguito River watershed and flows west, creating Lake Sutherland.

From the dam to its mouth, the river flows through the long and narrow San Dieguito River Park past Del Mar, and broadens into a tidal waterway and a 150-acre (0.61 km2) lagoon as it crosses under Interstate 5 and past the Del Mar Fairgounds to empty into the Pacific Ocean at Del Mar, California.

The San Dieguito River watershed has vast areas, over 83%, of open space.

Vegetation cover ranges from pine forest on the slopes of the headwater mountains to arid grassland on the plateaus and plains further downstream.

By the 16th century, most of the basin formed the southern part of the Luiseño tribal territory.