[2] The river forms in the northeastern corner of Manatee County and flows into the Gulf of Mexico at the southern edge of Tampa Bay.

Wildlife in and around the river includes alligators, herons, manatees, dolphins, and fish such as bass, bluegill, catfish, and gar.

[3] The Manatee River headwaters flow 45 mi (72 km) in a westerly direction towards the Gulf of Mexico and southern Tampa Bay.

[4] These locations cause the river to contain areas that are as varied as hardwood swamps, mesic flatwoods, coastal lowlands, and marshes.

Everything from finfish and invertebrates to bait and food shrimp is harvested from its waters, therefore, many commercial fishing regulations apply.

A few of the birds are considered threatened such as the snowy plover, bald eagle, Florida scrub-jay, and peregrine falcon.

The uprooting of the forested wetlands and uplands has caused excess nutrients to build up in the Bill Evers Reservoir.