The Grand meanders past fertile farm fields (almost 80% of the watershed is farmland), towns and cities and through rich wetlands, like Luther Marsh in its northern reaches. At Elora, the river tumbles over a 15-metre waterfall and rushes between sheer 25-metre limestone walls. Below the city of Cambridge, the river is bordered by long stretches of Carolinian forest composed of sycamore, black walnut, hackberry and other species rare in Canada. At Paris, where the Nith River meets the Grand, the Grand's southerly flow becomes more easterly.

Indigenous cultures have long prospered along the Grand. People hunted mastadon and bison here more than 10 000 years ago. The first European known to descend the river was the famous explorer René-Robert Cavelier de La Salle in 1669. To the early French settlers, the river was known as Rivière la Rapide or Rivière L'Urse, "Bear River." The name "Grand" first appears on a map from 1744.

Following the American Revolution, the Six Nations of the Haudenosaunee (Iroquois) Confederacy from Upper New York State received a land grant along the Grand in recognition of their loyalty to Britain. The town of Brantford stands near the river crossing named after their famous leader Joseph Brant. Mennonites from Pennsylvania in search of religious freedom settled near the present-day city of Waterloo. Many historic buildings, from rural homes to flour and textile mills, foundries and distilleries, still appear much as they did during their 19th-century heyday.

Nestled in the heartland of the most populated part of Canada, the Grand River is important for recreation and tourism. Its upper reaches are known for world-class fishing for brown trout; paddling is popular all along the river; and the most extensive system of hiking trails in Ontario winds along its banks. The well-preserved evidence of the cultures that were drawn to its fertile valley, the outstanding recreational opportunities it offers and its scenic beauty led to the inclusion of the Grand River in the Canadian Heritage Rivers System in 1994.