Coun Alan Law, who has been a Firth Park councillor for 30 years, is stepping down due to ill health.
He held his seat in the May local elections with a majority of 1,086 but announced he was leaving the council just three months later.
The Firth Park ward includes Longley and Southey Green plus the Flower, Stubbin and Brushes estates.
It is the second most deprived ward in the city, out of 28, according to council data. More than 35 per cent of children in Firth Park receive free school meals.
A by-election will take place on Thursday, September 16 with polling stations open 7am to 10pm.
Nominations to stand as a candidate must be submitted by Thursday, August 19.
In the May local elections, Labour, the Conservatives, the Liberal Democrats and the Green Party all stood candidates, along with an Independent.
Coun Law polled 1,896 votes, with his nearest rival the Conservatives who took 810 votes.
The former Lord Mayor and chairman of the planning committee said it had been a great honour and privilege to serve as a councillor.
“I’m really proud of the work we have done and I would like to thank everyone I’ve had the privilege of working with, particularly the local community.
“I still care passionately about serving the community and I wish whoever is lucky enough to be elected every success for the future, serving a brilliant community.”