In 1612, businessman John Rolfe successfully cultivated a non-native strain of tobacco which proved popular in England.

[7] Soon, the river became the primary means of exporting the large hogsheads of this cash crop from an ever-growing number of plantations with wharfs along its banks.

Below the falls at Richmond, many James River plantations had their own wharves, and additional ports and/or early railheads were located at Warwick, Bermuda Hundred, City Point, Claremont, Scotland, and Smithfield, and, during the 17th century, the capital of the colony at Jamestown.

[citation needed] Navigation of the James River played an important role in early Virginia commerce and in the settlement of the interior, although growth of the colony was primarily in the Tidewater region during the first 75 years.

The upper reaches of the river above the head of navigation at the fall line were explored by fur-trading parties sent out by Abraham Wood during the late 17th century.

Produce from the Piedmont and Great Valley regions descended the river to seaports at Richmond and Manchester through such port towns as Lynchburg, Scottsville, Columbia and Buchanan.

For the most mountainous section between the two points, the James River and Kanawha Turnpike was built to provide a portage link for wagons and stagecoaches.

In December 1975 Virginia Governor Mills Godwin Jr. shut down the James River to fishing for 100 miles, from Richmond to the Chesapeake Bay.

The Chesapeake Bay Agreement of 1983, signed by the governors of Maryland, Virginia, and Pennsylvania, the mayor of the District of Columbia, and the EPA, established baseline environmental protections and promoted regional cooperation conducive to river clean-up.

In their 2023 report, JRA concluded that the "overall grade of the State of the James has improved to a B with a score of 66% from its failing health decades ago.

From the river's start in the Blue Ridge Mountains to Richmond, numerous rapids and pools offer fishing and whitewater rafting.

The most intense whitewater stretch is a 2-mile (3 km) segment that ends in downtown Richmond where the river goes over the fall line.

Below the fall line east of Richmond, the river is better suited for water skiing and other large boat recreation.

Due to ocean-going shipping upriver as far as the Port of Richmond, a combination of ferryboats, high bridges and bridge-tunnels are used for highway traffic.