Between 1670 and 1870, the Hudson’s Bay Company was granted exclusive fur trading rights to the area drained by the rivers flowing into Hudson Bay, then called Rupert's Land.

The earliest significant human modification of the native prairie ecosystems was spurred by European demand for products of the fur trade, particularly those from bison. The killing of thousands of bison each year by European settlers led to the virtual elimination of free-roaming bison by the 1880s.

Settlement and landscape modification greatly increased after 1870, when the Hudson’s Bay Company surrendered its charter and sold Rupert's Land to Canada. To secure the area against potential encroachment by the United States, Canada encouraged land development. In the early part of this century, following the completion of the transcontinental railway in 1885, a massive migration saw more than 200 000 homesteaders stake their claims.

Railways played a leading role in defining the pattern of development. Towns emerged along the rail line as collection points for grain and livestock exports and as distribution points for incoming supplies. By 1916, Canada was leading the world in wheat exports. Twenty-five years later, 60% of the Prairies Ecozone was under cultivation and the landscape resembled a checkerboard.

In 1936, farmers represented 50% of the population. Today that number has fallen to less than 10%. Population decline in the rural areas and growth in the urban areas has been the general rule since the 1950s. Although urban use of land is tiny in terms of area (0.3%), it remains an important influence on the ecozone. Today, the proportion of the urban population is 81% compared with 76% for all of Canada, a remarkable figure given that agricultural activities dominate the landscape of this ecozone. In 1991, the total population of the Prairies Ecozone was approximately 3.8 million, an increase of 25% since 1971. The major population centres are Calgary, Edmonton, Saskatoon, Regina and Winnipeg.

The economic structure of the ecozone reflects a dependence on the primary industries of agriculture, mining, and gas and oil extraction. The Prairies provide 19% of Canada's total resource-based employment, with agricultural activities and food processing accounting for nearly 62% of the total. Its minerals industry (fossil fuels and related products) accounts for nearly a third of Canada's total employment in this sector. In 1991, the Prairies Ecozone had an estimated Gross Domestic Product of roughly $91 billion, representing about 15% of Canada's total GDP.

The Prairies Ecozone has been farmed with a limited variety of crops. Only 15 field crops (grain, oilseeds, and pulses) and even fewer forage crops occupy more than 95% of the cropped area. With the exception of canola, which has recently surpassed wheat in the amount of area seeded, these crops have been the mainstay of production since European settlement. Beef and dairy cattle, swine, horses, chickens, and turkeys are the primary domesticated animals.

Mining, particularly the production of fuels, is the second most important industry. Although the value of mineral production increased in both Saskatchewan and Alberta between 1976 and 1991, land use for oil production has declined over the past decade, reflecting changes in world prices and incentives for exploration and development. By 1991, the value of mineral production in the Alberta portion of the ecozone made up 46% of Canada's total mineral activity.

The Prairie economy is now shifting from primary and secondary industies toward service-based sectors. The primary and secondary industries are geared mainly at processing food, wood, metals, chemicals, and petrochemicals. In the 1980s, agriculture generated about $5 billion, or 25% of all exports from the region. This accounted for 2% of global grain, rice and vegetable oil output. Mineral and fossil fuel exploitation and other goods and services generate $15 billion annually.