[2] The creek shares its name with Santiago Peak, at 5,687 ft (1,733 m) the highest point in Orange County, on whose slopes its headwaters rise.

Historically the Santiago Creek provided water for the Tongva people, whose territory extended over much of northern present-day Orange County and into the Los Angeles Basin.

Once out of the national forest it passes through the town of Modjeska and meets the first major tributary, Harding Canyon Creek, from the right.

Past the first Santiago Canyon Road crossing, the gorge widens to a broad alluvial plain, where the valley walls pull away and decrease in height.

[4][5] Irvine Lake provides water to Villa Park and Orange via a pipeline and flume to Peters Canyon Reservoir.

[6] Below the dam the dry riverbed meets Fremont Canyon, a right bank tributary, and crosses underneath California State Route 241.

About 10 miles (16 km) below the confluence with Santiago Creek, the Santa Ana River enters the Pacific Ocean at Huntington Beach.

[4][5] The Santiago Creek watershed occupies much of the northwestern end of the Santa Ana Mountains, and is located generally north of the city of Irvine.

The northern portion of the mountains, which Santiago Creek drains, is composed of rocks from the pre-Triassic to the Quaternary (251–2.6 MYA).

[10] Before the latter 19th century, Santiago Creek and its tributaries were free flowing perennial streams spilling out of Santa Ana Mountains canyons onto the broad, alluvial floodplain.

coast live oaks (Quercus agrifolia), California sycamores (Platanus racemosa), white alders (Alnus rhombifolia), native willows (Salix species), and other riparian habitat vegetation lined the route of the creek and its primary tributaries.

The creek and adjacent habitats supported a wide variety of birds, amphibians, fish, insects, and mammals.

Most of the creek originally lay in the territory of the Acjachemen and the Tongva peoples, two large Native American groups of present-day Orange, Los Angeles, and San Diego Counties.

The Native Americans had been drawn to the area by the abundant riparian zone found along Santiago Creek and some of its perennial tributaries.

They ground the acorns in stone mortars carved into large boulders and rock formations, with some remaining in the creek's canyon areas.

[12] In 1769 the Spanish Portolá expedition, first European land exploration of Alta California, traveled northwest along the southern edge of the Santa Ana Mountains.

Padre Juan Crespi noted in his diary that the creek was named for the Apostle Santiago el Mayor".

The retaliation was one in a series against local Tongva (Gabrielino) Native Americans taking horses from the Mexican ranchos.

They followed hoofprints into Cañada de los Indios, came upon a Tongva village, massacred the native residents, and took the remaining horses.

[17] By the 1920s, the Orange/Anaheim/Villa Park area was a prospering agricultural region that depended on water from the Santa Ana River and Santiago Creek.

Santiago Creek would unleash seasonal floods in the winter and then while becoming a trickle or completely dry in the summer, making irrigation difficult.

The lower course of Santiago Creek ended up being channelized in the mid-20th century after the passage of the Orange County Flood Control Act of 1927.

However, 13 specimens of the land-locked form of steelhead, rainbow trout, were fin-sampled recently from Harding Canyon and genetic analysis has shown them to be of native and not hatchery stocks.

[6] The upper Santiago Creek watershed lies within the Trabuco Ranger District of the Cleveland National Forest.