A mock gravestone for Lough Neagh as well as banners which read "Water is Life" and "Save Lough Neagh" were carried during the procession from Writer's Square to City Hall on Saturday.
Activists from various environmental campaigns, political parties and trade unions joined with people living near Lough Neagh and anglers to highlight the crisis at the lough and "set out clear demands for its restoration".
The campaigners are demanding the public acquisition of the lough, an independent Environmental Protection Agency, investment in a research and recovery plan, the end of commercial sand-dredging and sewage dumping, a reduction in agricultural run-off and recognition of the rights of nature.
Lough Neagh is the biggest freshwater lake in the UK or Ireland. It supplies 40% of Northern Ireland's drinking water and sustains a major eel-fishing industry. Noxious blooms of blue green algae covered large parts of the lough across the summer.
Other waterways and beaches in Northern Ireland have also been affected by the issue.
Nitrogen and phosphorus from agricultural fertiliser running off fields is believed to be a major contributory factor.
The spread of the invasive zebra mussel species is also understood to have played a role, as they have made the water clearer, allowing more sunlight to penetrate, stimulating more algal photosynthesis.
Climate change is another factor cited, with the highest ever water temperature at Lough Neagh recorded in June.
Speakers at City Hall on Saturday included People Before Profit MLA Gerry Carroll, academic John Barry, campaigner James Orr and Louise Taylor of Love Our Lough.
Ms Taylor led the crowd in a pledge to work to protect the lough.
Mr Carroll called for "urgent action to address the environmental crisis at Lough Neagh".
"Coupled with a global climate crisis, Lough Neagh is being turned into a boiling cesspit," he said.
He claimed warnings from environmental campaigners were ignored by government, and also called for the lough to be brought into public ownership.
"Lough Neagh is a vital natural resource that should belong to us all," he said.
Mr Orr said all those gathered should not be called protesters but protectors. "The protesters are the people who are killing Lough Neagh, you're protectors, you're people who care for the lough," he said.
"To me, that's the foundation for going forward. Lough Neagh is our heartland in the middle of Northern Ireland, it needs justice, it needs a just settlement."
Mr Barry claimed that government has failed to protect Lough Neagh. "The Department of Agriculture, Environment and Rural Affairs, the Northern Ireland Environment Agency and Northern Ireland Water have all failed us," he said.
"When government breaks the social contract, it is not only our right but our duty to rise up and protest and make our voices heard."