Gambell is located on the northwest cape of St. Lawrence Island, 200 miles southwest of Nome, in the Bering Sea. The city is 36 miles from the Chukotka Peninsula, Siberia. Gambell is located in the Cape Nome Recording District. The area encompasses 10.9 sq. miles of land and 19.5 sq. miles of water.

St. Lawrence Island has been inhabited intermittently for the past 2,000 years by Yup'ik Eskimos. In the 18th and 19th centuries, over 4,000 people inhabited the island in 35 villages. Sivuqaq is the Yup'ik name for the village and for the island. The city was renamed for Mr. and Mrs. Vene C. Gambell, missionaries to the town. A tragic famine between 1878 and 1880 decimated the population. In 1900, reindeer were introduced to the island for local use, and in 1903 President Roosevelt established a reindeer reservation. During the 1930s, some residents moved to Savoonga to establish a permanent settlement there. The city was incorporated in 1963. When the Alaska Native Claims Settlement Act (ANCSA) was passed in 1971, Gambell and Savoonga decided not to participate and instead opted for title to the 1.136 million acres of land in the former St. Lawrence Island Reserve. The island is jointly owned by Savoonga and Gambell.

A federally-recognized tribe is located in the community -- the Native Village of Gambell. The isolation of Gambell has helped to maintain their traditional St. Lawrence Yup'ik culture, their language, and their subsistence lifestyle, which is based on marine mammals. Residents are almost completely bilingual. Walrus-hide boats are still used to hunt. The sale, importation, and possession of alcohol is banned in the village.