The Chollas Creek's four branches begin in the cities of Lemon Grove and La Mesa and empties into San Diego Bay at Barrio Logan.

The pollution levels are high enough that it is considered an "impaired" water body by the California Office of Environmental Health Hazard Assessment.

Plans to renovate the creek into a regional park began in 2002 and were completed in 2021 by the City of San Diego.

[7]: 4  Soils within the watershed are primarily of the Holocene-age, which overlay the older San Diego Formation, which was formed during the Pliocene-age.

This leads to increased volume and velocity of water during storms, which in turn has resulted in erosion of land impacting habitat and existing infrastructure.

[13]: 10–11  The maximum discharge predicted from the creek when it goes under Main Street, near Naval Station San Diego, is 21,000 cubic feet (590 m3) per second.

[14]: 77  Only a small portion of the watershed are tidelands, and fall under the jurisdiction of the Port of San Diego or the United States Navy.

[9]: 9 In the late 19th century, thickets of cactus as tall as nearly six feet high were noted in the valley created by the creek.

[6]: 12  Other species of plants observed growing abundantly included Arctostaphylos, Ceanothus, Eriodictyon californicum, Vitis girdiana, and Diplacus aurantiacus.

[6]: 12  By the late 20th century, species of plants found along the creek were Eriogonum fasciculatum, Salvia apiana, Quercus dumosa, Malosma, and Diplacus aurantiacus.

[17]: 26–27, 35  Other wildlife which might be found around the creek include desert cottontail, gray foxes, and big brown bats.

[18] Birds commonly found along Chollas Creek include the California gnatcatcher, red-tailed hawk, Bell's vireo, and cactus wren.

[6]: 9  At one point in its history, Chollas Creek had a confluence with the Sweetwater River, where these waters drained into the ocean through Silver Strand.

[6]: 53 During the Portola Expedition (1769-1770), a survey conducted by crew members of the San Antonio found that Chollas Creek was a viable water source.

[29]: H-43 [30][31] In 1851, Army officer Nathaniel Lyon traveled east along the creek and established a route to what is now Campo, California.

[6]: 40 [33] In 1886, the National City and Otay Railroad built a track and crossing over the creek near the present-day alignment of Main Street to supply the construction of Sweetwater Dam.

[43] Operated remotely from Point Loma, at the time of its creation it used the largest vacuum tube constructed, and required 50 US gallons (190 L) per minute to keep it cooled.

[46]: 2, 8 [47] It was built as one of a series of high-powered radio stations, including locations in Pearl Harbor, Cavite, and Annapolis.

[14]: 36  Beginning in the late 1970s volunteers began to conduct vegetation clearing in the City Heights neighborhood to reduce fire potential within the canyons which the creek flows through .

Improvements included "walking paths, native plant landscaping, mosaic art benches and shade structures".

[65] Due to debris that flows down Chollas Creek, it ends up in Naval Base San Diego, its publics works is responsible for the debris removal; in 2017, 46.97 short tons (42,610 kg) worth of trash was removed from the creek within the navy base.

[67] In June 2021, the City of San Diego declared that Chollas Creek would be made into a regional park.

[69] Prior to this, Chollas Creek was the only major waterway in San Diego not to be designated a regional park.

[73] One of the theories at the time was that he had traveled from San Diego Bay up Chollas Creek to Highway 94 – a route of 3.5 miles (5.6 km).

[73] The first time this particular sea lion required the assistance of SeaWorld personnel was in November 2021, when it had made its way away from the water onto Harbor Island Drive near San Diego International Airport.

[75][78] In 2016, San Diego Fire-Rescue Department noted that Chollas Creek was at risk for flooding due to El Niño related storms.

[83] In 2022, before Tropical Storm Kay arrived to San Diego, an emergency declaration was made, and part of the Chollas Creek was cleared of vegetation and debris in the Southcrest and Shelltown neighborhoods, removing over 2,000 short tons (1,800,000 kg) worth of material.

[90] A City of San Diego official later stated that the rains that occurred on January 22 exceeded the design of the stormwater channels within the Chollas Creek watershed.