Club Mission, a sprawling venue under the railway arches on Heaton's Court, has been a stalwart of Leeds' nightlife scene for more than 17 years.
In a statement issued on Friday, the club announced it would cease trading 'until further notice' due to the pressures of the Covid-19 pandemic.
It is believed Mission's adjacent sister club, Tunnel Leeds, will also close its doors.
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In the statement, a Mission spokesperson said: "The current global crisis regarding Covid-19 is forcing businesses to make sad decisions that affect daily life and the livelihoods of our management, staff, promoters, entertainers and DJ's.
"It is with a heavy heart and deep filled sadness that we have to close our business until further notice.
"This decision is based on doing the right thing for you our loyal customers, our amazing managers, our incredible staff and our unbelievable entertainers and DJs.
"The safety of everyone is paramount during these uncertain times.
"Until we party again, stay safe and be kind to each other."
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o each other."