Upper Kalskag is a traditional Yup'ik village, with a culture centered on subsistence activities. The founding residents were from the native village of Kaltkhagamute, four miles down river. The Russian explorer Lavrenty Zagoskin reported a population of 120 in 1843 for Kaltkhagamute (Khalkagmute). Over the years, residents of Crow Village, Ohagamiut, Russian Mission, and Paimute also moved to the village. Russian and American explorers brought both Roman Catholic and Russian Orthodox religious influences, but the village's Russian Orthodox practitioners left to establish Lower Kalskag 2 miles downriver in 1940. George Morgan, a German immigrant who founded Georgetown, established a general store and post office in 1932. Paul N. Kameroff, Sr. also established a general store, a pool hall, and a coffee shop around 1930. The government school was built in that timeframe as well. The community once owned a herd of about 2000 caribou.
