After the creek leaves the canyon it flows through Bryn Mawr and Loma Linda to its mouth on the Santa Ana River, near the I-10 and I-215 interchange.

[2] Historically, San Timoteo Canyon was used as a travel corridor by Native Americans and Spanish ranchers.

[9] In the 19th century the village of Saahatpa was established in San Timoteo Canyon by Chief Juan Antonio and his band of Cahuilla Indians.

The federal government made appropriations for channelization of the entire creek in 1988, but local opposition to the measure was strong.

The United States Army Corps of Engineers has built flood control structures along most of the lower reaches of the creek.

[1] The Environmental Protection Agency, in cooperation with San Bernardino County, Redlands, and Loma Linda, are working to restore sections of San Timoteo Creek's riparian ecosystem to a close approximation of its natural state, while recognizing it is not possible to restore certain reaches to a pristine condition.

[1] San Timoteo is one of the last major drainage systems in the inland area of Southern California with some significant remnants of riparian vegetation and habitat.