When the United States entered the war with Germany on 11 December, Greenland became a warring nation. Remaining contact with Copenhagen was broken off, rationing and daylight saving time was introduced, and local currency and stamps printed. In 1942, the U.S. Army took over protection of the Ivigtut mine, and combat patrols began to be flown from Bluie West One, which became the headquarters for both the Coast Guard Greenland Patrol (now directly under the U.S. Navy) and the U.S. Army Air Force (USAAF) Greenland Base Command. A third air base was established at Bluie East Two during the summer. The Greenland population, which had been 18,000 natives and fewer than 500 Danes, was augmented by thousands of U.S. servicemen. Relations with the Americans were excellent, as they provided news, provisions, humanitarian aid, and entertainment in addition to greatly expanding the island's infrastructure.[citation needed] In 1944 a five kroner coin was struck in Philadelphia, largely for the use of U.S. GIs. Greenland's commercial interests in North America were maintained by the Greenland Delegation with the aid of Kauffmann and Svane. Brun remained in Greenland as head of a unified administration.

German weather stations
Beginning in August 1942, the Germans established four clandestine weather stations on the east coast. The first expedition on Sabine Island was detected in the spring, but was withdrawn successfully before it was attacked. The fall 1943 expedition at Shannon Island also operated successfully over the winter and spring and was withdrawn by air. Two expeditions in October 1944 were seized by the Coast Guard before they could get established.

The German weather station Holzauge at Hansa Bay on the northeast coast of Sabine Island was discovered by a team from the Sledge Patrol on 11 March 1943. The Germans realized they had been discovered, and gave chase to the team, who had to abandon their equipment (including their dog teams) and retreat to the station at Eskimonæs, to warn Ib Poulsen, the Sledge Patrol commander.

Poulsen reported the German base to the Greenland government on 13 March 1943, and asked for automatic weapons and further orders. Governor Brun officially designated the patrol the "Army of Greenland" and named Poulsen its captain, effective 15 March.

The Germans attacked Eskimonaes on 23 March. Before help could arrive they seized and burned the station. Though unhurt, the entire Sledge Patrol contingent based there was forced to make a 400-mile trek to the station at Ella Island without sleds, food, or equipment. On their way back to Sabine, the Germans ambushed a three-man patrol at Sandodden, killing the leader, Corporal Eli Knudsen.

In late-April, Lieutenant Hermann Ritter, the officer in command of the German detachment , was taken prisoner by the Sledge Patrol and brought to the Americans after a long journey to Scoresby Sound.

The German base on Sabine was bombed by USAAF bombers from Iceland. It was then seized by a Coast Guard landing party, but all German personnel save one person had already been evacuated by a Dornier Do 26.[16] Apart from fire exchanged between German aircraft and U.S. ships, this was the only offensive air attack on the Greenland mainland. An American air force formation attacked the station on 14 May to make sure it could be of no use to the Germans.

Two more skirmishes occurred between the Sledge Patrol and the Germans, leaving the Greenland force with two more dead and four wounded by the end of conflict in 1944.

The last German weather station, Edelweiss II, was captured by U.S. Army forces and its crew taken prisoner on 4 October 1944. The American troops landed from the icebreaker USCGC Eastwind, which later transferred the prisoners to USCGC Storis. The German transport ship Externsteine, which was resupplying the station, was seized by Eastwind, renamed Eastbreeze and commissioned in the United States Coast Guard.

Greenland played an important role in North Atlantic air traffic during the war, but the island's role as a major base for anti-submarine warfare assets was hampered by adverse weather, winter darkness, and difficult logistics. For a long period, a flight of six PBY Catalinas of VP-6(CG) was maintained at Bluie West One, carrying out a great variety of missions.