It was formed between 1825 and 1831 and included historical Bedford County, Lower Canada.
The name of the county is derived from an Algonquin Abenaki language word meaning "lots of waterfowl"[citation needed].
Missisquoi County, part of the Eastern Townships (one of roughly 12 regions in Québec), is located on the western fringes of the Appalachian foothills, giving it a rolling landscape on its eastern part.
The westernmost point of the county is on the Richelieu River at the Canada–US border at 45° N and 73°20′ W. The county is divided into four townships, and there are two discontinuous zones along its western fringes without any township designation divided under the pre-1760 French parochial framework.
The county seat is the Town of Bedford located at 45°7′ N and 72°59′ W in the southwestern part of the Township of Stanbridge.