The river flows northeast and becomes the boundary between York County and the city of Poquoson, reaching Chesapeake Bay just north of the Plum Tree Island National Wildlife Refuge.

The Poquoson River became a strategic location for both sides during the Peninsula Campaign early in the Civil War.

A Confederate garrison that became known as "Camp Misery" due to its swampy location was established at Ship Point where Chisman Creek meets the Poquoson River near its mouth.

General John Bankhead Magruder and the Army of the Peninsula were charged with attempting to stop McClellan.

This line was not intended to completely stop the Union soldiers, but to stall them long enough for other fortifications to be built and additional reinforcements to arrive.

On April 4, 1863 Colonel William Averill and his 3rd Pennsylvania Cavalry were sent to reconnoiter Ship Point's garrison and defenses.

Steamers that had been converted to hospital ships were anchored in Chisman's Creek and the Poquoson River.

After Yorktown fell Ship Point was no longer needed as a supply depot or embarkation site.