Publisher Trinity Mirror said the Liverpool Post is to cease publishing next week, with its final edition on December 19.
The company said there are no planned journalist redundancies, with the newspaper continuing its business coverage in a section of the Liverpool Echo.
This is a decision we take with the heaviest of hearts. Sadly, the Liverpool city region no longer generates the demand in terms of advertising or circulation, to sustain both the Post and the Liverpool Echo.
The newspaper ceased daily publication in January 2012 when it became a weekly.
That the Post has lasted as long is testimony to generations of brilliant and committed journalists who have worked on it.
''We have a history of brave and independent journalism and excellent coverage of business, arts, and sport. We will ensure we keep those traditions alive within the Liverpool Echo.''
More top news
A Liverpool fan who died in the Hillsborough disaster asked when the crush was going to stop, his inquest has hear
Detectives investigating the murder of Pc David Phillips have arrested two people on suspicion of murder.
The Transport Secretary Patrick McLoughlin says the £44 million revamp of Victoria Station is proof of the Northern Powerhouse.