The airport opened in 1920, and until 1932, the site was the bypass highway that ran from Tenth Avenue to Eighteenth Avenue. The airport served as a stopover for aircraft including United States Army Junkers JL-4's and de Havilland Fours going to Alaska. In 1932, the airport was moved to the intersections of Highway 97 and Highway 16, near Carney Hill (the same site is now the Prince George Golf and Curling Club). At this second, newer airport, US planes also flew in large numbers to Alaska prior to the United States declaring war on Japan. Planes seen included Douglas B-18's and Martin B-10's. This airport was used until about 1942 and was closed for good on March 31, 1944. During the 1930s and early 1940s, it contained Pineview Elementary School, which was renamed the Airport School.

In approximately 1942 the aerodrome was listed as D of T Aerodrome (old)- Prince George, British Columbia at 53°54′N 122°46′W with a variation of 28 degrees E and elevation of 1,900 ft (579 m). The aerodrome was listed with two runways as follows:

On November 14, 1940, the Canadian-American Permanent Joint Board of Defence set out a need for multiple new northwest airports, including Prince George, to support the new Northwest Staging Route. This new staging route would provide protection, permit aircraft to be deployed rapidly to northwestern Canada and Alaska in time of emergency and allow men and supplies to be moved into the region by air.

In late 1940, Canada's Department of National Defence contracted to build a new (third) Prince George airport on a bench at the top of the hill about 3 mi (4.8 km) south-east of the city on the old Cariboo Highway, across from the Federal Government's Experimental Farm. This location is now the site of today's airport. The Department of Transport built single family homes, an unmarried staff residence, a diesel electric power plant and vehicle maintenance garage. A small administration building and radio range station was built by Pan American World Airways (Pan Am) and a few years later (1944) this was replaced by a new, larger DOT administration/radio range terminal and a large hangar was built (it burned down in 2009) about the same time. The resident DOT staff were housed on the airport and the Pan Am staff were accommodated in houses built on the east side of the old Cariboo highway, across from the airport.

In 1942, the United States Army Air Forces started construction on a number of buildings for their staff and for Royal Canadian Air Force staff, including troop dormitories, a medical clinic, a gymnasium and a cafeteria. The latter was also used for USO shows and movies for airport staff. The US staff component included an Army Airways Communication Station, an Eleventh Air Force detachment (1452nd AAF Base Unit - detached from Edmonton Municipal) and a small detachment of United States Navy staff. The US Navy had a contract with Pan Am to fly men, equipment and everything else from Seattle to Juneau and Fairbanks via Prince George and on to Kodiak (Naval Air Station Kodiak), Dutch Harbor (Dutch Harbor Naval Operating Base), Adak (Naval Air Facility Adak) and back in periods when coastal weather conditions were poor. The Eleventh Air Force's 1452nd Base Unit at Prince George airport were Air Transport Command, charged with facilitating aircraft and supply shipments from the contiguous United States to Alaska on the Northwest Staging Route.

The new airport comprised 2,034 acres (823 ha), was completed on August 9, 1945, and had three runways arranged in a triangle.

In 1941, after the completion of runway 14/32 (now 15/33), US-based Pan Am operated from the Prince George Airport as a stopover location on its Seattle to Fairbanks route ferrying men and equipment for the US Navy. In 1942, Canadian Pacific Air Lines (CP Air) began offering scheduled flights six times a week into Prince George. Canadian Pacific and its successor Canadian Airlines International served the airport for many years. Between 1942 and 1944, the airport was used as an alternate airport (to Edmonton Municipal) by the United States Army Air Forces (USAAF) for United States to the Soviet Union Lend-Lease aircraft flown primarily from Great Falls, Montana to Alaska and on to the Soviet Union. Planes seen in the new Prince George airport were mostly P-39 Airacobras, P-63 Kingcobras, B-25 Mitchell bombers, and C-47 Skytrain transports. Also seen were RCAF Hawker Hurricanes and Bristol Fairchild Bolingbroke bombers.

In approximately 1942 the aerodrome was listed as RCAF Aerodrome - Prince George (new), British Columbia at 53°54′N 122°40′W with a variation of 28 degrees E and elevation of 2,225 ft (678 m). The aerodrome was listed as "Under construction - Field Serviceable" with three runways as follows:

During the Second World War, the RCAF operated the airport in close assistance with the Department of Transport and the USAAF. In 1946, with the war over, the airport was turned over to the Department of Transport by the RCAF and the USAAF and RCAF buildings were torn down, leaving the DOT buildings and homes as well as the Pan Am housing.