Flowing Northeast through East England to its mouth at Lutton Marsh into The Wash in the North Sea, the Nene and its tributaries drain an area of about 2,270 square kilometres (880 sq mi), with a population of 750,000.

The earliest known examples, which date back to the 10th century AD, have been linked to Indo-European root words for snow, rain, or washing, but a direct connection is purely speculative.

From Dodford, the river passes through the village of Weedon where it flows under the main west coast railway line, the Grand Union Canal, and Watling Street.

Three of these streams supply water for reservoirs at Pitsford, Hollowell and Ravensthorpe, north of Northampton, before joining the Brampton Nene.

[17] At Earls Barton the river again passes an area of mature gravel pit lakes, and lock gates numbers 9 and 10.

[18] The river's course turns to the north-east, passing the town of Wellingborough on its north bank and the village of Little Irchester to the south.

The river now passes under a viaduct that carries the Midland Main Line, which links London St Pancras to Sheffield in northern England via Luton, Bedford, Kettering, Leicester, Derby and Chesterfield.

1⁄2 mile (800 m) upstream of the city centre is Woodston Wharf—the site of the old sea lock—originally the extent of the tidal River Nene until the Dog-in-a-Doublet lock at Whittlesey was opened in 1937.

The branch terminates, for navigation, at Stanground Lock, a connection to the Middle Levels, the drainage system of the Fens through which access is possible to the River Great Ouse.

Continuing downstream leads to the 'Embankment' area and after the cathedral city itself, passing through Whittlesey the landscape changes to the Nene Washes in The Fens and their vast horizons.

Most leisure use is between Northampton and Peterborough, where it makes a junction with the Middle Level Navigations at Stanground Sluice, which give access to the River Ouse.

c. 19) was obtained, which appointed large numbers of Commissioners, but stated that work could only proceed if any nine of them could find someone to make the entire river navigable.

Robert Wright and Thomas Squire agreed to these terms for the section from Peterborough to the bridge at Oundle North in September 1726, and completed the work by 1730.

The river opened to navigation in stages over the next three years, with a great celebration being held at Northampton on 7 August 1761 when the work was completed.

[23] Tolls rose to a little over £1,000 per year, but the Commissioners decided that the canal boats damaged the locks, and all traffic had to be transferred to river barges.

The main problem was a restriction at Wisbech, and the engineer James Rendel estimated that £120,000 was required to reconstruct the river below Peterborough.

In order to improve the mouth of the river, which followed a tortuous route through salt marshes, the construction of a new channel was proposed by Nathaniel Kinderley, and work started on it in 1721.

c. cxxviii) gave the commissioners wide powers to manage the river, but created an administrative structure that was too complex to be workable.

With the river in a poor state, James Rendel was appointed as engineer, and began dredging the channel and raising the banks, which cost £124,000.

Wisbech Corporation took the Commissioners to court in 1859 for obstructing the river, and when an initial judgement was made in their favour, gangs of men destroyed most of the Waldersea dam overnight.

An appeal to the Court of Chancery by the Commissioners also failed, and the dams were removed, as was the Wisbech weir, after an accident involving a train of lighters.

A dock covering 13 acres (5.3 ha) was built at Sutton Bridge at this time, but the outer wall collapsed on 9 June 1881, a few days before it was officially opened, and the estimated repair costs of £160,000 resulted in the project failing.

This arrangement permits the use of the locks as additional weirs in time of flood, when the mitre gates are chained open and the guillotines lifted to allow the water to flow straight through.

In recent years the Environment Agency, who are the navigation authority for the river, have been installing electric operation of the guillotines[34] and in some cases replacing them altogether with mitre gates.

The Nene was badly affected, flooding low-lying parts of Northampton, Wellingborough, Earls Barton and other settlements on its banks.

[45] In 2007, the Government announced it would spend £6 million on flood defences at Upton Mill in the west of Northampton; wetland areas and embankments were to be constructed along the river.

[46] In December 2013, the 2010 £12 million project to protect 10,590 residents and 1,200 businesses with an improved flood defence regime prevented another major incursion of water.

[47] In 2016, composer, Benjamin Till was commissioned by NMPAT (Northamptonshire Music and Performing Arts Trust) to create a major orchestral and choral work about the Nene.

[48] The composition was scored for 800 musicians and premiered at the Royal Albert Hall in 2017, before being performed at Northampton's Derngate Theatre and Peterborough Cathedral.

The piece quotes tradition folk melodies from towns and villages along the river, and explores ghost stories, myths and legends associated with the Nene.