St Just Chapel - completed in 1833 - will close its doors for worship in August 2017.
The church joins a list of closures in the county due to falling congregation numbers and rising maintenance costs.
President of the Methodist Conference, Reverend Steven Wild, said the decision reflected a "changing society".
"It is really sad. They built it so everybody in the community could fit in it to hear the gospel message.
"Times have changed. The way that people worship is different now... Unfortunately secularisation has crept in in our country in quite a big way that we don't see in other parts of the world."
Julian Drew, superintendent minister for West Penwith, said the costs of maintaining the building were "quite huge".
"It's a big building... [The costs] are beyond the size of the congregation that's here".
Mr Drew said the church council would be looking at "a number of options" for the future of the chapel over the coming months, but that if no group came forward to support its upkeep the building would have to go on the market.
The Miners Cathedral got its name in remembrance of 20 people who lost their lives when the West Wheal Owles mine flooded in 1893.
A Methodist chapel in Cornwall, sometimes known as the Miners' Cathedral, will close next year it has been announced.