ATIK, on Commercial Street, says it will shut after the Jubilee Weekend.
A spokesperson for the club said the reason for closing is "the business has not recovered since lockdown".
The pandemic forced many businesses to close for months on end during several lockdowns, with nightclubs among the last to reopen each time.
The club has thanked the thousands of people who have visited over the years.
It has posted on social media: "Yes, it’s true – we’re closing
"Next week really is the end of an era for us and we’d love to see you one last time for our final Royal Farewell!
"From the bottom of our hearts, we would like to thank the many thousands of guests who have supported us over the years and helped create so many happy memories.
"We plan to go out with a bang over the Jubilee Weekend and hope all our loyal customers will join us for one last dance as we say farewell to ATIK and clubbing as we know it in Halifax.
"Finally, we would like to thank our employees who work so hard and who have been through so much with the pandemic and we are truly sorry we can’t keep the club going. You’ve been amazing."
Dozens of fans of the club have been expressing their sadness.
One posted: "Met my hubby upstairs in Maine Street. Many a fond memory in there.
Another said: "Best night out in Halifax."
The building that used to be Coliseum, and then Liquid and Main Street, became ATIK in 2016.
ATIK is holding 'Royal Farewell' nights between Wednesday, June 1 and Saturday, June 4.