It flows westerly from its source at Dyken Pond, located in the town of Berlin, to its mouth at the Hudson River in the city of Troy.

[3] The Poesten Kill begins at Dyken Pond, a man-made body of water located in the Petersburg Mountains about 20 miles (32 km) east of the Hudson River.

[4] Dyken Pond is fed by local streams and springs and is located near the corners of the towns of Grafton, Berlin, and Poestenkill at an elevation of 1,624 feet (495 m).

[7] The next major tributary is Sweet Milk Creek, which begins as a stream in north central Brunswick and travels about 4.7 miles (7.6 km)[7] before combining in the southwestern portion of the town.

The first permanent European settlement in the area was Fort Orange, a trading post built by the Dutch West India Company in 1624, about 10 miles (16 km) south of the mouth of the creek.

[10] However, the mouth of the Poesten Kill at the Hudson is said to be first genuine European frontier settlement outside the barricades of Fort Orange.

[13] Van Rensselaer named the land surrounding the mouth of the Poesten Kill Pafraets Dael after his mother, Maria Parfait.

[15] While most of the settlements along or near the Poesten Kill during the Dutch era revolved around farming, some were also based on easy access to the Mohicans for trade in fur.

[17] At the time, the fur trade was legally monopolized by the Dutch West India Company, so this practice was illegal but very profitable.

[21] In the 1800s, many mills and factories were built along this river to use waterpower or have easy access to the Hudson on a riverside road beginning just after Poesten Kill Falls.

However, the vicinity poses inherent risks due to its proximity to rapids formed by creek flows post-floods or winter thaws.

In February 2017, a young individual fell, was reported missing, and was discovered deceased in the Hudson River two months later.

A private company has a small power station that still produces electricity from hydropower on the north side of the river that was built in the 1950s[25] and used turbines inside the remains of the concrete foundation of the old industrial mills.

This road leads to a small dirt path tangled with saplings and roots along old industrial remains from the Marshall Factories.

During the winter, the colder weather brings snow cover to much of the surrounding banks, and a thick layer of ice forms across the river.