Volunteers cleared almost 170 bin bags worth of rubbish, five mattresses, four sofas and more from the banks of the River Roding in Ilford last weekend.
Organiser Paul Powlesland said it was the most rubbish “ever collected by a long way” since litter picks began four years ago.
He added Friends of the River Roding, a group of boaters and residents aiming to clear the land near the North Circular, previously found sex toys among the rubbish dumped by the river.
The group hope that, once cleared, Transport for London will agree to reopen the land as a public pathway between Ilford and Barking.
Mr Powlesland said: “One area was effectively being used as a rubbish tip.
“The rubbish came up to waist height and some of it dropped below the water line so it could potentially have been washed into the river, which is not good.
“We are doing this really because we want to reopen this path between Barking and Ilford as a walking route. Our eventual aim is for a beautiful, rubbish-free river.
“Hopefully, lockdown dependent, we will be doing another one early next month and we will just keep doing this until we get rid of it all.”
Friends of the River Roding, who have a Facebook group with more than 1,000 members, have completed around a dozen litter picks so far.
Just over a year ago, the group set up the River Roding Trust, funded by a voluntary licence fee paid by boaters that live on the river.
The Trust plans to use some of this money to repair fencing along the North Circular, in order to discourage future fly-tippers.
In April, Mayor of London Sadiq Khan said he “fully supports” the hard work the Trust does for the community.
He said: “This work will provide a welcome complement to TfL’s significant investment in walking and cycling in the area.
“I have asked Transport for London to contact the Environment teams in the local authorities the River Roding runs through; namely Epping Forest, Redbridge, Newham and Barking and Dagenham.
“They will ask them to make contact with the trust to offer assistance on any restoration works that they can support.”