Upper Kalskag is a Central Yup'ik Eskimo village located on the north bank of the Kuskokwim River, two miles upriver from Lower Kalskag. It lies in the Yukon-Kuskokwim Delta, 30 miles west of Aniak and 99 miles northeast of Bethel.

The village was a fish camp called "Kessiglik" in the late 1800's." Around 1900, residents of "Kalthagamute" began to move to Kessiglik and the village grew. In the 1930's the Bureau of Indian Affairs established a government school there and the village grew more. In 1940 the Kameroff family established a general store, post office, coffee shop and barging company in the community. At this time, the community owned and worked a herd of 2,100 reindeer.

During the 1930s, Russian Orthodox practitioners in the village relocated to establish Lower Kalskag, two miles to the southwest. The villagers who remained were primarily Roman Catholic practitioners. The city was incorporated in 1975. As of 2011, Alaska Department of Labor Estimates put Upper Kalskag's population at 219. Subsistence activities remain an important component of the Yup'ik lifestyle. Salmon, moose, rabbit, and waterfowl are the primary resources. A few residents maintain gardens.

Upper Kalskag has had a Roman Catholic flavor since its early days. Baptisms were performed there as early as the 1890's. Catholic Church activity became more regular around 1900 when missionary priests of the Society of Jesus began visiting from Holy Cross Mission. The original church was built there in 1926, and a new one built in 1965. Records indicate that the mission was dedicated at first to the Sacred Heart. As late as 1954 that was the case. However, by 1981 it had been dedicated to the Immaculate Conception and has remained so since. The Society of Jesus continued to serve the Upper Kalskag community, sometimes in residence but more often in visits from other villages, into the 1980's. Since then priestly visits have been made by Diocesan priests, including priests from Poland serving in the Diocese of Fairbanks, and by Franciscan priests.

Since the 1990's, religious sisters have also been an important Catholic presence in the village including Sisters of Notre Dame and Sisters of St. Joseph.

In recent years, parishes in the Yukon-Kuskokwim Delta area of the Catholic Diocese of Fairbanks have been served on a rotating schedule by ministry teams which may include priests, deacons, and religious and trained lay staff members. Immaculate Conception is served by ministers of Y-K Subregion B.