It flows south to southeast, and drains about 1,950 square miles (5,100 km2) of southwestern Connecticut into Long Island Sound.

[8] Samuel Orcutt, a 19th-century historian, explained the term's pronunciation as "more properly...Howsatunnuck" and also noted an early spelling in the form of "Oweantinock".

[12] The river passes through land that was formerly occupied primarily by native people of Algonquian lineage, typically living in villages of two to three hundred families housed in hide wigwams.

[10][13] These native inhabitants burned the forests along the Housatonic Valley in the autumn to keep the underbrush down, a practice which was customary throughout Connecticut prior to European settlement.

[14] One notable native was Chief Squantz of the Schaghticoke tribe, who still hold a portion of the former reservation on the west side of the Housatonic River, in what is now called the town of Kent.

[15] Lydia Sigourney's poem The Housatonic is in her volume, Scenes in my Native Land, 1845, where it accompanied by descriptive text on the river and its neighbourhood.

Inspired by the river during his honeymoon, the American classical music composer Charles Ives wrote "The Housatonic at Stockbridge" as part of his composition Three Places in New England during the 1910s, drawing his text from a poem of the same name by Robert Underwood Johnson.

In 1969, nine-year-old Thom Reed and his family claimed to see a bright light rise from the Housatonic River, then found themselves inside "what appeared to be an airplane hangar," where they saw creatures that "resembled large insects."

From circa 1932 until 1977, the river received PCB pollution discharges from the General Electric (GE) plant at Pittsfield, Massachusetts.

[24] Although the water quality has improved in recent decades, and some remediation has taken place,[25][26] the river continues to be contaminated by PCBs.

[27] Between 2005 and 2018 GE completed remediation and restoration of the 10 manufacturing plant areas within the city, and continues to conduct inspection, monitoring and maintenance activities.

The highest concentrations of PCBs in the Housatonic River are found in Woods Pond in Lenox, Massachusetts, just south of Pittsfield, where they have been measured up to 110 mg/kg in the sediment.

[29] Birds, such as ducks, and fish that live in and around the river contain significant levels of PCBs and can present health risks if consumed.

[30][31][32][33] Negotiations regarding how to clean up the contaminated areas south of Pittsfield had continued for many years since the initial Superfund site designations, involving GE, EPA, local governments, citizen groups and other stakeholders.

[39][better source needed][40] High mercury levels are measured in the sediment at the outflow delta of the Housatonic River into Long Island Sound.

[41] The Housatonic River watershed drains 1,948 square miles (5,050 km2) in western Connecticut and Massachusetts and eastern New York.

[42] The Housatonic River is a popular whitewater paddling destination beginning at Falls Village, Connecticut, and continuing to Gaylordsville.

[43] Lake Housatonic is used by the Yale University Crew Team at the Gilder Boathouse and by the New Haven Rowing Club.

The most popular area for fly fishing is in Litchfield County, Connecticut, between the dam at Falls Village and Cornwall Bridge.