Once navigable from the bay inland to the vicinity of Mission Dolores, where several smaller creeks converged to form it, Mission Creek has long since been largely culverted. Its only remaining portion above-ground is the Mission Creek Channel which drains into China Basin. The only other location where Mission Creek can still be seen is below-ground in the basement of the San Francisco Armory.
The two Ramaytush Indian villages of Chutchui and Sitlintac were located on Mission Creek.
Declared by the state legislature in 1854 to be a navigable stream, it retains the designation today, even though most of it was vacated for use by boats in 1874 and later filled in.
The China Basin Building was erected on the creek's north bank in the 1920s and used for off-loading and processing bananas through the 1950s. In the 1970s it was known as the Del Monte Building and used as a food distribution site by the Hearst family in response to the demands of the SLA.
A community of house boats has existed along the creek's south bank since 1960 when the state of California moved the houseboat community there from Islais Creek to make way for merchant ship trading.
The mouth of Mission Creek has been known to Major League Baseball fans as McCovey Cove ever since the year 2000 when the San Francisco Giants relocated from their former home at Candlestick Park to AT&T Park on the creek's north bank. Balls hit over the right field wall splash-land in the water there.
- Nancy Olmsted, Vanished Waters: A History of San Francisco's Mission Bay (San Francisco: Mission Creek Conservancy, 1986) ISBN 0961149213
- Nancy Olmsted, Chris Carlsson, Bob Isaacson, Vanished Waters: A History of San Francisco's Mission Bay 2nd ed., rev. (San Francisco: Mission Creek Conservancy, 2010)
- Vanished Waters of Southeastern San Francisco by William Crittenden Sharpsteen
- Water Water by Chris Carlsson
- Mission Creek by Chris Carlsson