The lake, its shores populated by the Assiniboine and Cree, was made known to Europeans by La Vérendrye in the mid-1730s.

He and his sons travelled from Fort La Reine through this lake to explore the Saskatchewan River and its environs.

The name derives from Cree manitou-wapow or Ojibwa manidoobaa, both meaning "straits of Manitou, the Great Spirit", a toponym referring to what are now called The Narrows in the centre of the lake.

The southern tip of the lake, 24 kilometres (15 mi) north of Portage la Prairie, Manitoba, ends in the Delta Marsh, an important staging ground for migrating birds.

Communities on the lake include Fairford, Steep Rock, St. Laurent, and Sandy Bay.

In 1933 following dry years in the late 1920s and early 1930s, the Province constructed a concrete control dam across the Fairford River immediately downstream of the channel.

However, beginning around a level of 248 m (813 ft) ASL, localized flooding of agricultural land around the lake can occur.

[19] The main marketable fish species caught on Lake Manitoba has changed from whitefish in the late 19th century to walleye, sauger and yellow perch today.