With Ernest de Koven Leffingwell, he organized the Anglo-American polar expedition which wintered off Flaxman Island, Alaska, in 1906–07. They lost their ship, but in a sledge journey over the ice, they located the continental shelf of the Arctic Ocean, 65 miles (105 km) offshore, where in a span of 2 miles (3.2 km), the sea's depth increased from 50 meters (160 feet) to more than 690 meters (2,260 feet).[2]
Mikkelsen organized an expedition to map the northeast coast of Greenland and to recover the bodies of the ill-fated Denmark expedition leader, Ludvig Mylius-Erichsen, and cartographer, Niels Peter Høeg Hagen, in addition to their records. For this task, Mikkelsen wintered from 1909 to 1910 at Shannon Island. His wooden ship, the Alabama, became trapped in the ice of Shannon Island and, while he was exploring, the rest of the party returned home on a whaler. Remaining with his engineer, Iver Iversen, Mikkelsen succeeded through a series of hazardous sledge journeys. They recovered the lost records in a cairn at the head of Danmark Fjord, discovering that "the Peary Channel does not exist."[3]
Hence, he rebutted the existence of a hypothetical sound or marine channel running from east to west separating Peary Land in northernmost Greenland from the mainland further south.[3]
The two explorers returned to Shannon Island to find the crew gone, but they used salvaged timbers and planking to erect a small cottage. Mikkelsen and Iversen then spent two winters at the cottage before they were rescued, in the direst of extremities, by a Norwegian whaler in the summer of 1912.[2] The so-called Alabama cottage has survived and was photographed during a visit by the Danish Navy inspection ship Ejnar Mikkelsen in September 2010.[4]
In 1924, he led an expedition to settle what later came to be Scoresbysund.[2] In 1932, he led the "Second East-Greenland Expedition of the Scoresbysund Committee" that carried out the first archaeological excavations on the Skaergaard intrusion by the shores of the Kangerlussuaq Fjord.[5]