[1] The base was named in honour of Sir William Pepperrell (1696–1759) of Kittery, Maine, commander of a force of 4,200 soldiers and sailors aboard 90 ships, who captured the French seaport at Louisbourg after a 46-day siege on June 16, 1745.

Of particular importance was Newfoundland, which the United States sought to arm as a buffer area similar to Alaska territory.

One of the locations under consideration for a military base was St. John's, the capital city, which was approved by Newfoundland Governor Sir Humphrey T. Walwyn.

Several steps had been taken by the British and Newfoundland governments pre-dating the official signing of the agreement, which identified the preferred site for a military installation along the north side of Quidi Vidi Lake, in the northeast part of St. John's.

On March 27, 1941, the United States officially signed the Lend-Lease agreement which gave possession of the site for the installation; construction work began in earnest soon afterward.

On May 20, troops from the 3rd U.S. Infantry Regiment quartered aboard USAT Edmund B. Alexander began moving into their new temporary camp.

The reasons behind the apparently slow pace of construction for the base was likely related to the fact that the United States did not enter the war until late 1941.

By contrast, the more deliberate pace set by the still-neutral US military saw their construction in Newfoundland planned for a much more substantial investment, intended to last the length of the 99-year lease.

Lt. Col. J.J. Yates assumed command of Fort Pepperrell on November 28, 1941, and was replaced on December 2 by Colonel Paul N. Starling.

In January 1941 part of Battery A, 57th Coast Artillery (Tractor Drawn) (TD) Regiment with two mobile 155 mm guns probably arrived on USAT Edmund B. Alexander.

[14] Fort Pepperrell expanded significantly after the United States entered the war with the attack on Pearl Harbor in December 1941.

Beginning with the 21st Signal Service Company, the US military began to link up Edmund B. Alexander with the temporary shore establishments.

One such difficult link in the cross country communication line was the 110-mile (180 km) stretch from Stephenville to Port aux Basques.

St. John's Harbour, one of two ice-free ports on the island during the winter months, was engaged in unloading supplies necessary to maintain the Newfoundland garrisons.

On February 27, 1942, the headquarters for the Newfoundland Base Command had moved from temporary quarters at 44 Rennie's Mill Road on the estate of the country's former prime minister, Sir Richard Squires.

Peacetime left the future of the Newfoundland Base Command and Fort Pepperrell unclear, since the deactivation of units and redeployment of forces had been going on at a rapid pace.

The USAF constructed two 25,000-square-foot (2,300 m2) aircraft hangars as well as a 36,000-square-foot (3,300 m2) machine shop and administrative offices at the airfield to support Pepperrell AFB.

Following the Korean War, the late 1950s saw the importance of Pepperrell AFB decline as the US military consolidated its Newfoundland facilities in light of changing threats and technology employed by the Soviet Union and the Warsaw Pact.

In a 6-month period in 1956, 862,500 miles (1,388,100 km) were driven, using 93,900 gallons of gasoline, and the base handled requests for 18,560 taxi trips.

The 138th Engineer Aviation Group, SCARWAF (Special Category Army With Air Force) was inactivated on May 31, 1956, along with its 15 officers and 70 enlisted men.

The Engineer Aviation Battalion remained at Pepperrell AFB and was placed under the control of the US Army from Governor's Island in New York City.

Each pilot of the 6604th ABW was required to put in 100 hours of flying on an annual basis, divided equally between the first and second half of the fiscal year.

In 1955, cross-island flights to the North American mainland were begun as a means of testing the pilots proficiency and making full use of the airplanes.

On May 15, 1961, the last American forces departed Pepperrell AFB when the United States Army Transportation Terminal Command Arctic closed its headquarters.

On August 10, 1961, the American flag was lowered at Pepperrell AFB and the Union Jack and the Canadian Red Ensign were raised as the base property was transferred back to the Crown.