Activists are urging the federal government and premiers to work together to protect Australia's largest lake - Lake Eyre - and the rivers that feed it.

The Australian Floodplain Association (AFA) says the expansion of mining and irrigation are posing the biggest threats to the Lake Eyre Basin in decades.

About 100 graziers, indigenous people, scientists and policy experts have been attending a three-day conference at Longreach in outback Queensland, which ended on Wednesday.

The delegates have sent a communique urging Queensland Premier Campbell Newman, South Australia Premier Jay Weatherill and federal Environment Minister Tony Burke to work together to prevent "the disaster of the Murray Darling river system being repeated".

Conference organiser and member of the Queensland government's Western Rivers advisory panel, Professor Richard Kingsford, says the basin is the "beating heart of Australia".

"Lake Eyre is fed by some of the last healthy, unregulated river systems on Earth," he said in a statement.

"Any type of irrigation and mining would cause permanent damage and local communities have now made their concerns very clear."

The communique also calls for the creation of a Lake Eyre Basin Rivers Management Act.