Two permanent Coast Miwok villages were located on San Antonio Creek: Meleya (southwest of Petaluma, California) and Amayelle.

[3] San Antonio Creek is one of many California places named by the early Spanish colonists after Saint Anthony of Padua, a patron of the Franciscan Order.

The creek traverses the Rancho Laguna de San Antonio land grant, dated May 6, 1839 and November 25, 1845, given by Governor Pío Pico to Bartolomé Bojorquez in 1845.

This diversion is 5.2 miles (8.4 km) upstream from its historical connection to the San Antonio Slough just west of Hog Island in the wetlands south of Petaluma, California.

[7] The largest striped bass ((Morone saxatilis)) ever landed with tackle and line was caught in 1912 by Charles R. Bond in San Antonio Creek, weighing 87 lb 8 oz (39.7 kg) and 5 ft 9 in (1.75 m) long, according to a photograph in the Marin Rod and Gun Club.