The creek runs for 45 miles (72 km) from a lake northeast of Packard Ridge to the eastern shore of San Francisco Bay by way of Niles Canyon and a flood control channel.

Within the watershed can be found some of the highest peaks (Mount Isabel and Mount Hamilton) and tallest waterfall (Murietta Falls) in the East Bay, over a dozen regional parks, and notable natural landmarks such as the cascades at Little Yosemite and the wildflower-strewn grasslands and oak savannahs of the Sunol Regional Wilderness.

Completion of a series of dam removal and fish passage projects, along with improved stream flows for cold-water fish and planned habitat restoration, enable steelhead trout and Chinook salmon to access up to 20 miles (32 km) of spawning and rearing habitat in Alameda Creek and its tributaries.

[3] The first juvenile trout migrating downstream from the upper watershed through lower Alameda Creek toward San Francisco Bay was detected and documented in April 2023.

To geologists this is evidence that it is an antecedent stream that existed prior to the rise of the East Bay hills about a million years ago.

The large alluvial fan under Fremont, Newark, and Union City which juts into San Francisco Bay is further evidence that this creek has been in place for a very long time.

[17] Alameda Creek is considered a potential ‘anchor watershed’ for steelhead, regionally significant for restoration of the threatened trout to the entire Bay Area, although by the late 1950s the California Department of Fish and Game decided the steelhead run was no longer viable due to numerous man-made barriers to fish runs.

[13] Since steelhead in the Bay Area and California's Central Coast were listed as threatened under the Endangered Species Act in 1997, numerous organizations, including the Alameda Creek Alliance, and governmental agencies have cooperated on restoration projects to allow migratory fish from the Bay to reach spawning habitat in upper Alameda Creek, beginning in 1999.

[20] In 2009, the Alameda County Water District removed a rubber dam that blocked trout passage in the lower creek, adjacent to Quarry Lakes Regional Park.

[21] The goal was that when those projects were completed in 2021, steelhead would be able to migrate upstream to spawning habitats in the Sunol Valley for the first time in a half-century.

[17] Recent physical evidence has proved that the southern limit of coastal Chinook salmon included the southernmost tributaries of South San Francisco Bay.

La Framboise stated that "the Bay of San Francisco abounds in beaver", and that he "made his best hunt in the vicinity of the missions".

[25] Alexander Roderick McLeod reported on the progress of the first Hudson's Bay Company fur brigade sent to California in 1829, "Beaver is become an article of traffic on the Coast as at the Mission of St. Joseph alone upwards of Fifteen hundred Beaver Skins were collected from the natives at a trifling value and sold to Ships at 3 Dollars".

[27][28] Physical evidence of beaver include faunal remains in the Arroyo de la Laguna tributary recovered in an archaeological site west of Interstate 680.

[34] Downstream of San Francisco's dams, the Alameda Creek Alliance has helped to initiate the removal of 11 barriers to fish passage since 2001.