The Duke of Northumberland's River was one of seven environmental projects to win a share of £900,000 after going head to head in an online poll.
More than 10,000 people voted in the Mayor's Big Green Poll to decide which schemes were most deserving of the Greater London Authority cash. Of those, 1,754 plumped for the Duke's River, making it the third most popular project.
A restoration project at Stanmore Marsh was among the other successful schemes.
FORCE (Friends of the River Crane Environment) said the money for the Duke's River would be topped up by Hounslow and Richmond councils and other bodies to a total of £400,000.
It will be spent tidying up existing paths and opening new ones along the 4km stretch of water between Twickenham's Kneller Gardens, where it meets the River Crane, and Isleworth, where it runs into the Thames.
The investment will also be used to clean up the river, which already supports wildlife including kingfishers and water voles, and to promote it to the public. The improvements will help create a new 10km circular riverside walk linking the Crane, Thames and Duke's rivers.
The Duke's River was built more than 500 years ago to feed ponds at Syon Priory, where Syon Park now stands, and it used to power a number of mills.
Today much of it is unloved and largely forgotten, with many sections hard to reach or overgrown and covered with litter, hence its description in the poll as "little known".
The Crane Valley Partnership and the environmental charity FORCE teamed up to suggest the project, which they hope will lead to a ten-fold increase in the number of visitors.
FORCE chairman Rob Gray said: "We are extremely grateful to all those who voted for this project and helped to win this funding. This project is a huge opportunity to improve the environmental and community value of the Duke's River corridor and create a wonderful new asset for the boroughs of Hounslow and Richmond."
Work is due to start this April and be completed next year. FORCE will be part of a steering group overseeing the project, which will be managed by Hounslow and Richmond councils.
Jean Rolfe, who chairs the Crane Valley Partnership, said: "We are delighted that our proposal has been so well received and very much wish to thank all those that voted for the project. We are very excited and can’t wait to get started bringing about much needed change that will enhance the river corridor for both people and wildlife."
Although the seven schemes were competing for the money, such was the level of support London mayor Boris Johnson decided to give each a portion of the prize pot.
A restoration project at Stanmore Marsh, in Harrow, was one of two initiatives to get £175,000. The money will be used to create around 3,000sq-m of wetlands at the site, helping to prevent flooding and acting as a haven for plants and wildlife.
More than four hectares of land there will also be turned into an attractive green open space, and there will be nature trails and opportunities for local schoolchildren to learn about the environment through pond-dipping and other activities.