Vauxhall Motors FC have tended their resignation to the Football Conference to take effect from the end of the current playing season.
A statement from chairman Alan Bartlam says Vauxhall, like many other football clubs, are confronted with" the reality of low gates and ever-increasing costs."
Mr Bartlam said this now unsustainable position has been going on for several years despite the tremendous efforts of a dedicated and active committee to try and balance the books.
He said: "It is anticipated this season will result in another sizable financial loss eating into a legacy of finances that we were fortunate to inherit over a decade ago.
"And to do nothing would be foolhardy."
The chairman said the club's responsibilities go beyond the Football Conference - to some 30 teams, youth, junior and ladies, as well as catering for more than 400 children within Ellesmere Port and beyond.
"As a responsible committee administering a club that was founded over 50 years ago - and a club that we would wish to continue for another 50 - it has become necessary to withdraw the senior side from the established pyramid," he said.
"We have enjoyed 19 fabulous seasons in that pyramid, but now we must restructure, stabilise and rebuild again."