The multinational company has notified 1200 workers that after 60 years mining copper in the far northwest Queensland city, underground operations and the copper concentrator will close.
"Glencore has conducted a range of studies and reviews seeking to further extend the life of the underground copper mines but unfortunately it has not been possible and they have reached the end of mine life," the miner said in a statement on Wednesday.
"The studies revealed the remaining mineral resources are not economically viable due to low ore grades and areas where, due to geological conditions, safe extraction can't be achieved using current technology, this all coupled with ageing infrastructure."
The company said it's Lady Loretta zinc mine 140km northwest of Mt Isa will also close in 2025.
Chief Operating Officer Sam Strohmayr said it was disappointing the mine's life had reached its end and the company wanted to give affected workers and their families time to prepare.
He said it was too early to determine how many of the 1200 Mt Isa employees would receive redundancies.
"Our focus over the coming months will be to work closely with our people and contractors, our suppliers and the Mount Isa community to provide support as we move towards closure of these assets," he said.
"Redundancies are the last resort and will be offered only when other options have been exhausted."
The Australian Workers' Union called the decision an incredibly sad day for the Mount Isa community.
Queensland secretary Stacey Schinnerl said she had contacted Treasurer Cameron Dick to leave "no stone unturned" in providing support to members of the community and affected workers.
"This is a fight for Mount Isa, the capital of the northwest minerals province and the epicentre of the next mining boom," she said in a statement.
"We will do everything in our power to hold the government and Glencore to account in delivering the support and dignity that the Mount Isa community deserves."
Glencore said Mount Isa Mines' other metals assets including the copper smelter, George Fisher Mine, zinclead concentrator, the lead smelter and the copper refinery in Townsville will all continue operating.
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