He was the guide and climbing leader of the first complete ascent of Denali in 1913, with expedition members Hudson Stuck, Walter Harper and Robert Tatum.

He also carried freight and mail with Charles McGonagall via dog teams among the frontier towns of Fairbanks, Valdez and Kantishna, being paid $75 per month.

[5] Authorities required each "stampeder" (the persons intending to stay and mine) to bring in two tons of supplies to provide for himself for a year in the camps.

[6] Drawing on his skills developed on the frontier, from 1906 to 1908, Karstens accompanied Charles Sheldon, a hunter, conservationist, and naturalist, on hunting trips into the Toklat River region.

Sheldon, the chairman of the influential Boone and Crockett Club,[7] successfully campaigned with Congress to have the area set aside as a national park.

[8] On March 27, 1912, Hudson Stuck, Episcopal Archdeacon of the Yukon, sent Karstens a letter inviting him to join an expedition to climb Denali.

[10] In addition, two Gwich'in youths from Stuck's mission school, Johnny Fredson and Esias George, supported the party by managing its dog teams, and in base camp by hunting for meat and organizing supplies.

[11] (Fredson later became the first Alaska Native to graduate from college and was a lifelong leader of the Gwich'in people, founding their Venetie Indian Reserve in 1941).

A previous expedition had called it "step [sic], but practicable,"[13] so Karstens and Stuck were surprised to find huge chunks of rocks and ice in their path.

Looking at the North Summit through field glasses, they saw a flagstaff set up by Thomas Lloyd and three other men; his party had reached it three years earlier.

[16] They spent an hour and a half on the summit, during which Robert Tatum planted the American flag he had made earlier from red, white, and blue handkerchiefs.

[12] While they were still at base camp, Stuck sent out a messenger to announce their success, claiming credit as leader of the expedition, and it was published in The New York Times on June 21.

[2]: 266 [17] Highly recommended by Charles Sheldon, Karstens was appointed as the first superintendent of the newly established Denali National Park, serving from 1921 to his resignation in October 1928.