Below Doncaster, the main channel of the lower Don originally meandered in a north-easterly direction across the marshland of Hatfield Chase to enter the Trent just above its junction with the Ouse. A second channel flowed to the north, along a Roman channel called Turnbridgedike. The eastern channel formed the boundary between Yorkshire and Lincolnshire.
In the Hatfield Level drainage project which started in 1626, the Dutch civil engineer Cornelius Vermuyden diverted the Don northwards along Turnbridgedike. He constructed Dikesmarsh bank some distance to the east of the channel, so that the intervening land could be used as washlands. The main work was completed by 1628, but after flooding in 1629, a "Great Sluice" was constructed at the junction between the river and the Aire, with 17 openings which were 6 by 8 feet (1.8 by 2.4 m), probably by Hugo Spiering, who had assisted Vermuyden on the main project. The washlands had insufficient capacity, and in 1632 work started on a new channel, which would run for 5 miles (8.0 km) from Newbridge, near Thorne, eastwards to enter the Ouse at the site of Goole, 9 miles (14 km) upstream of the Trent. Water levels here were between 5 and 10 feet (1.5 and 3.0 m) lower than at Turnbridge. This new channel was called the "Dutch River", and was finished in 1635, at a cost of £33,000. It ended in a sluice at Goole, and was never intended to be navigable, as boats could access the Aire at Turnbridge. The sluice was later swept away in a flood and never replaced.
The Dutch River was difficult to navigate, made more hazardous by shoals, three awkward bridges, and low water levels at neap tides. With the opening of the Stainforth and Keadby Canal in 1802, from the Don at Stainforth to the Trent at Keadby, most traffic for the Trent used that in preference to the Dutch River and the route around Trent Falls, where the Trent joins the Humber. Construction of a railway from Doncaster to Goole in 1869 reduced traffic on the river, but the Sheffield and South Yorkshire Navigation Company was formed in 1889, to buy back the River Don Navigation, the Sheffield Canal and the Stainforth and Keadby Canal from railway ownership, to keep them competitive. They acquired the waterways in 1895, but failed to raise sufficient capital for the major improvements they had planned. However, they succeeded in constructing the New Junction Canal from Stainforth to the Aire and Calder Navigation (Knottingley and Goole Canal) west of Goole, which was jointly funded by the Aire and Calder, and opened in 1905. The Dutch River reverted almost entirely to its original drainage function, and Stainforth lock, which connected it to the Stainforth and Keadby Canal, was closed in 1939.
Navigation to Sheffield was made possible by the construction of weirs, locks and canal cuttings to avoid circuitous and unnavigable sections of the Don downstream of Tinsley, and then by a canal from Tinsley to Sheffield. The first serious attempts at improvements were authorised by an Act of Parliament obtained in 1726 by Sheffield's Company of Cutlers to make the river navigable from Holmstile in Doncaster to Tinsley, on the edge of Sheffield, and another obtained by the Corporation of Doncaster in 1727 to improve the river below Holmstile, as far as Wilsick House in Barnby Dun. An Act of 1733 created "The Company of the Proprietors of the Navigation of the River Don", and authorised further cuts above Rotherham, while a further Bill of 1740 sought powers to improve the river from Barnby Dun to Fishlake Ferry, to avoid the shallows at Stainforth and Bramwith. The river was navigable to Rotherham in 1740, and to Tinsley by 1751.
Stainforth was connected to the River Trent by the opening on the Stainforth and Keadby Canal in 1802 and to the Aire and Calder Navigation by the New Junction Canal, opened in 1905. There were plans to use compartment boats to carry coal on the navigation, but although some locks were lengthened around 1910, Long Sandall lock was not, and it was not until 1959 that it was extended to 215 by 22 feet (65.5 by 6.7 m) and trains of 17 compartment boats could work through to Doncaster. The navigation was the subject of one of the last major attempts in the UK to attract commercial freight to the waterways. In 1983, it was upgraded to the 700-tonne Eurobarge standard by deepening the channels and enlarging the locks as far as Rotherham. The expected rise in freight traffic did not occur, however.
The cuts and navigable river sections, with the Stainforth and Keadby and the New Junction canals constitute the Sheffield and South Yorkshire Navigation. Locks on the Bramwith to Rotherham section can accommodate boats which are 230 by 20 feet (70.1 by 6.1 m), but above that, boats are restricted to 56 by 15 feet (17.1 by 4.6 m) by the short Rotherham lock.
The Don has produced some notable floods. On the night of 26 October 1536 a sudden rise in the level of the river prevented the forces of the Pilgrimage of Grace from crossing the river at Doncaster, forcing them to enter into negotiations with Henry VIII's forces. The Great Sheffield Flood, which occurred on 11 March 1864 following the collapse of the Dale Dike Dam on a tributary of the River Loxley, destroyed 800 houses, destroyed or damaged most of the Don bridges upstream of Lady's Bridge (see "Bridges over River Don" section below) and killed 270 people.
The Don was also one of the rivers that flooded during the 2007 United Kingdom floods. Following high levels of rainfall, some 80 million cubic metres of rain fell on South Yorkshire on 25 June 2007. The river burst its banks in the late afternoon, flooding areas of Sheffield from the Wicker to Meadowhall, and two people died after being swept away by the water. Parts of Rotherham and Doncaster were flooded for the second time in 10 days. Two days later, the army were called in to assist at Barnby Dun after the river flooded large areas near Thorpe Marsh Power Station.
The River Don catchment was the subject of extensive research investigations in the early 2000s, led primarily by the Catchment Science Centre, based at the University of Sheffield. A comprehensive summary of the river catchment was completed in 2008, describing the key social, economic and environmental characteristics of this historically important urban river and its main tributaries.