The river has two separate branches which converge near the intersection of Danforth Street and Winthrop Street (U.S. 44) in Rehoboth, Massachusetts to form the main branch of the river.
The west branch (officially West Branch Palmer River) rises in a small unnamed pond near the eastern intersection of Tremont Street and Agricultural Avenue in Rehoboth.
It continues roughly south from here until converging with the east branch.
After the two branches converge, the river flows roughly south-southwest through Rehoboth and Swansea before crossing into Rhode Island and flowing between Barrington and Warren for its last few miles.
The Palmer River is a subject of an 1885 painting by local artist Edward Mitchell Bannister.