It flows through the town of Mariposa then southwest through the Sierra foothills, into and across the San Joaquin Valley in Merced County, and empties the sloughs of the San Joaquin River south of the city of Merced.

Mariposa Creek was named by the Spanish explorer Gabriel Moraga on September 27, 1806, when his expedition discovered a great cluster of butterflies ("mariposas" in Spanish and Portuguese): Each year on the first weekend in May, Mariposa residents mark the annual arrival of migrating monarch butterflies with a "Butterfly Days" festival and parade.

During the California Gold Rush, the Mariposa River was a rich gold-bearing creek and the site of several mining camps, including Logtown, Mariposa and Mariposita.

Mariposa County contains three major drainage basins: the Merced River, Chowchilla River/Fresno River, and a localized cluster of streams of the east valley known as the Lower Mariposa group of streams.

These three basins and their component watersheds are part of the much larger San Joaquin River system that drains the western slopes of the Sierra Nevada.