Westchester County Airport was built during World War II in 1942 as a home to an Air National Guard unit to protect New York City and Rye Lake, part of the city's water supply system. In May 1983, with the growth of suburban Westchester and a strategic shift from defensive operations to cargo missions, the Guard unit abandoned Westchester Air National Guard Base and moved to Stewart International Airport, in Orange County.

The first scheduled airline flights were by American Airlines in late 1949 with a weekday morning flight from New York LaGuardia Airport (LGA) to HPN continuing to Syracuse Hancock International Airport (SYR) and beyond and returning in the evening. Mohawk Airlines replaced American in 1955; Mohawk and successor Allegheny Airlines served HPN until 1979. The first scheduled jet flight was a Mohawk BAC One-Eleven in 1965. According to the March 1, 1967 Mohawk system timetable, the airline was operating nonstop BAC One-Eleven jet service to both Rochester, NY (ROC) and Newark International Airport (EWR) as well as direct one stop BAC One-Eleven flights to Buffalo, NY (BUF) and also direct one stop BAC One-Eleven flights from Toronto (YYZ). Before the federal Airline Deregulation Act in 1978, the airport was being served in 1976 by Allegheny Airlines BAC One-Elevens and by several commuter air carriers including Air Speed, Command Airways and Commuter Airlines. Air Florida arrived in 1980 and United Airlines during the mid-1980s. American Airlines also resumed mainline service. Regional carrier Independence Air ceased operations at HPN on January 5, 2006.

Major airlines that previously served the airport include American Airlines, Northwest Airlines, Republic Airlines (1979-1986), United Airlines and USAir (now part of American Airlines). New start up carriers Air Florida, AirTran Airways, Carnival Air Lines, Midway Airlines and New York Air also served the airport. AirTran Airways began service at the airport in 2006 with flights to Atlanta, Orlando and West Palm Beach. These flights ended on August 11, 2012. Smaller regional and commuter air carriers that previously operated flights included Air North, Altair Airlines, Business Express Airlines, Boston-Maine Airways (operating as Pan Am Clipper Connection), Brockway Air, Command Airways, Commuter Airlines, Continental Express (now United Express), Empire Airlines, Independence Air, Island Air, Mall Airways and USAir Express. These airlines operated the following jets to the airport:

Air Florida – Boeing 737-200

AirTran – Boeing 717-200

Allegheny Airlines – BAC One-Eleven

American Airlines – Fokker 100

Carnival Air Lines – Boeing 737-200

Continental Express – Embraer ERJ-135 (operated by ExpressJet for Continental Airlines)

Empire Airlines – Fokker F28 Fellowship

Midway Airlines – Douglas DC-9-10

Mohawk Airlines – BAC One-Eleven

New York Air – McDonnell Douglas DC-9-32

Northwest Airlines – McDonnell Douglas DC-9-30

Northwest Jetlink (operated by Mesaba Airlines on behalf of Northwest Airlines) - Avro RJ85

Republic Airlines (1979-1986) – McDonnell Douglas DC-9-30

United Airlines – Boeing 737-200, 737-300 and 737-500

USAir – Fokker 100

In the summer of 1981 Air Florida's timetable listed international nonstop Boeing 737-200 service to Bermuda from the airport.

In June 2005, a drunken teenager and two of his friends stole a Cessna 172 from nearby Danbury Municipal Airport around 1 a.m. and landed on a taxiway at Westchester County Airport around 4 a.m. The aircraft was low on fuel and allegedly flying erratically. HPN airport was closed at the time and no runway lights were illuminated. Police arrived on the scene and reported beer bottles falling out of the aircraft as they arrested the teens, all of whom were charged with various felonies relating to the unauthorized use of the aircraft, theft, and alcohol impairment.

JetBlue began service at the airport in 2007 and is currently the airport's largest carrier by scheduled passengers.

In June 2009, Cape Air commenced service to Westchester with flights to Martha's Vineyard and Nantucket in Massachusetts. They then introduced service to Lebanon (NH) in early 2010. In Summer 2022, they eliminated all flights out of White Plains except for subsidized essential air service routes from Lebanon.

In May 2011, the New York State Department of Transportation published the "New York Statewide Airport Economic Impact Study," highlighting the economic impacts of public-use airports in New York state for fiscal year 2009. The study noted that HPN was one of only three airports in the state that increased its enplanements, surpassing the U.S. benchmark. It also noted that the cumulative economic activity for the airport was approximately $736 million.

On April 27, 2020, the airport was closed to general aviation traffic for one week and commercial airlines for about a month so Runway 16/34 could be repaved, a project originally scheduled to span four months with construction only occurring from midnight to 6 AM. This decision was made in the midst of COVID-19 pandemic-related air travel cuts, which drastically reduced commercial airline service to the airport.