San Bernard River flows from a spring near New Ulm, Texas[1] to its mouth on the Gulf of Mexico, some 120 miles (190 km) to the southeast of the source.

[1] It passes through portions of Austin, Brazoria, Colorado, Fort Bend, Matagorda and Wharton counties.

It passes alongside the Attwater Prairie Chicken National Wildlife Refuge, which shelters one of the last populations of the critically endangered Attwater's prairie-chicken, a ground-dwelling grouse of the coastal prairie ecosystem.

[1] Its mouth was impeded in 2005 causing it to drain into the Gulf Intracoastal Waterway, but was later corrected.

The river runs near several communities, including West Columbia, Texas and along the San Bernard National Wildlife Refuge.