[1] The community was known by several alternative names, including Kanas-nu, Kanasnu, Kenasnow and Killishoo.

Killisnoo Island has long been inhabited by Tlingit people.

In the late 1800s, the North West Trading Company built a fish processing plant at Killisnoo and many Tlingit moved from nearby Angoon and other areas to Killisnoo to work at the plant.

The plant was destroyed in a fire in 1928 and most of the residents left Killisnoo.

[2] Like nearby Angoon, Killisnoo receives less rain than most of southeastern Alaska.