The lake is fed by dozens of small rivers, including the Ashuapmushuan, the Mistassini, the Péribonka, the Des Aulnaies, the Métabetchouan, and the Ouiatchouane. The towns on its shores include Alma, Dolbeau-Mistassini, Roberval, Normandin, and Saint-Félicien.
The lake was initially named Piékougami (Flat Lake) by the Kakouchak Innu who lived on its shores. It was given its French name after Jean Dequen, a Jesuit missionary who in 1647 was the first European to reach its shores.
Industry on the lake was dominated with the fur trade until the 19th century. Colonization began in the Saguenay-Lac-Saint-Jean region in the early 1800s and continued intensively until the early 20th century. Industry was mainly forestry and agriculture. In the 20th century, pulp and paper mills and aluminum smelting rose to importance, encouraged by hydroelectric dams at Alma and on the Péribonka River. Lac Saint-Jean also has an important summer resort and sport-fishing industry.