Aviation at the site began in the 1920s as a grass strip, which was later improved by the Civilian Conservation Corps (CCC) and Works Progress Administration (WPA); the runway was first paved in 1946, and lengthened to 6,800 feet (2,070 m) in 1968 with an 1,800-foot (550 m) extension to the west.

Horizon Air (marketed and sold as Alaska Airlines) is the sole commercial airline serving the airport, flying Embraer 175 jet aircraft. Its limited service to Pullman–Moscow began 45 years ago in December 1981 with Fairchild F-27 aircraft (Friday & Sunday), and daily service (along with Lewiston) in March 1983, on F-27 and Metroliner aircraft. Service to Portland, Spokane, and Boise was ended in 1997.

Horizon (later folded into the Alaska brand) now offers four to five daily scheduled flights to Seattle–Tacoma. Historically, flight schedules had sometimes included a stop at Lewiston, but currently all scheduled flights to Seattle are non-stop. Flights to Boise returned August 2021 with service five times a week; it was suspended in May 2024 and is scheduled to return in August due to a lack of demand outside of the school year. Alaska moved to all-jet service to Pullman–Moscow in November 2022, replacing Q400 turboprops with Embraer 175 jets.

Prior to Horizon, Cascade Airways (1969–1986) was the main carrier at the airport, starting Palouse service in late 1971, and had over 16,500 boardings at Pullman–Moscow in 1977. Hughes Airwest supplied service in the early 1970s, and United Express for over two years, from May 1988 to September 1990.

From the late 1960s to the mid-1970s, a regional airport for the Quad Cities (Lewiston–Clarkston, Moscow–Pullman) was explored, but the city council of Lewiston withdrew its support of the study in October 1974. Lewiston–Nez Perce County Airport is about 25 miles (40 km) south.