The area received its first permanent settlers around 1770. The town of Lake Luzerne was set off from the town of Queensbury in 1792 as the "Town of Fairfield." In 1808, the town changed its name to "Luzerne," and in 1963 to "Lake Luzerne". Now known more for its Lake Luzerne Chamber Music Festival, artists such as classical guitarist Joel Brown, the Imani Winds, violinist Raymond Gniewek, and jazz greats Chris and Dave Brubeck perform during the summer months.

• Beartown – A hamlet in the eastern part of the town.
• Danielstown – A hamlet in the south part of the town in the vicinity of Daniels Road and County Route 32 (Call Street).
• Fourth Lake – A hamlet west of a lake by the same name and north of Lake Luzerne hamlet on Route 9N.
• Hartman – A hamlet in the south part of the town, east of Danielstown, in the vicinity of Hartman Loop and County Route 32 (Call Street).
• Lake Luzerne – A hamlet on the east bank of the Hudson River on Route 9N. It is south of a lake also called Lake Luzerne and by the west town line.
• Lake Luzerne-Hadley – A census-designated place in the towns of Lake Luzerne and Hadley.
• Lake Vanare – A hamlet east of Fourth Lake on Route 9N. It is next to a lake, Lake Vanare.