It rises from Echo Lake, in the town of New Castle south of the hamlet of Millwood, and flows generally southwest past Briarcliff Manor to its outlet at Sleepy Hollow.

[7][8] Another 1,200 feet south of that crossing, it recrosses Saw Mill River Road just north of where it merges with the Briarcliff–Peekskill Parkway (also State Route 9A).

[9] After a slight swing east towards the Taconic, the river crosses under the parkway for the last time and continues on a more southwesterly course past 420-foot (130 m) Beech Hill into 164-acre (66 ha) Pocantico Lakes Park.

It widens amid swampy areas on either side as it receives Caney Brook from the north and then becomes Pocantico Lake.

Midway along the lake, the municipal boundary leaves the river, putting it entirely within the town of Mount Pleasant.

At Old Sleepy Hollow Road it enters Rockefeller State Park Preserve, at over 1,400 acres (570 ha) the largest of the three protected areas the river flows through.

After another quarter-mile (400 m) it crosses under the Old Croton Aqueduct, a National Historic Landmark (NHL), and leaves the preserve, continuing straight through a steep, narrow wooded ravine in a slightly southwesterly direction.

[12] As it flows between Sleepy Hollow Cemetery to the west and the village's Douglas Park to the east, the river drops below 50 feet (15 m) in elevation.

[14][15] From that outlet, it meanders northwest past the former Tarrytown Truck Assembly plant, widening into a flood plain as it does.

[14][15] The Pocantico's 16-square-mile (41 km2) watershed covers areas of Ossining, Mount Pleasant, and New Castle, including Briarcliff Manor and Sleepy Hollow.

[24] A ship called the Roebuck, which transported cargo to and from New York City, ended up in the river, where its keel was scavenged by the miller at the mill of the Philipsburg Manor House site.

[4] In 2014, $9.9 million was put aside to repair the Tarrytown sewage treatment plant in order to improve water quality in the region.

The river met state standards on nitrate and phosphate levels, resulting in little cultural eutrophication in the water.

[42][b] As well, Washington Irving makes frequent mention of the Pocantico River in Chronicle III of his short story anthology Wolfert's Roost.

[43] The delighted historian pursued his explorations far into the foldings of the hills where the Pocantico winds its wizard stream among the mazes of its old Indian haunts; sometimes running darkly in pieces of woodland beneath balancing sprays of beech and chestnut: sometimes sparkling between grassy borders in fresh green intervals; here and there receiving the tributes of silver rills which came whimpering down the hill sides from their parent springs.

In a remote part of the Hollow, where the Pocantico forced its way down rugged rocks, stood Carl's mill, the haunted house of the neighborhood.