A large part of the territory was occupied during the Antiquity by the Diablinthes whose capital was Noviodunum (Jublains). Part of the area around Château-Gontier was controlled by the Andes tribe.
During the Middle Ages, the history of Mayenne was closely tied to that of most of the Maine territory and to that of Anjou (Craon and Château-Gontier areas). Indeed, these areas were all under the control of the Plantagenets when they acceded to the crown of England in the 12th century.
In 1429, Guy XIV was the first lord of Laval to become a count under Charles VII.
Laval was the birthplace of the counter-revolutionary Chouannerie movement in 1793. The royalists (occupying Laval at the time) defeated General Léchelle's republican army in heaths of the Croix-Bataille area, only to evacuate the city, recaptured by the republicans, a short time afterwards.
After the two World Wars, Mayenne rekindled its devastated economy by an intense modernisation of agriculture, thus boosting the food industry, and by investing in technical domains such as printing and publishing.