The Wheatsheaf pub in Tooting Bec is in danger of becoming a generic supermarket, according to campaigners and MP Sadiq Khan.
Wandsworth Council's planning committee is due to meet on Tuesday night to make a decision over its future.
Campaigners are calling for an Article 4 direction to be granted against the change of use, following the fight to ward off supermarket giants and luxury flat developers last year.
Tooting MP Mr Khan said: "The council has now had several chances to save the Wheatsheaf pub, and just like last time, it looks like they are going to bottle it.
"Instead of standing up for thousands of local residents they appear to be on the side of greedy developers.
"With the local elections over they are arrogantly ignoring the views of thousands of local residents.
"This means a much-loved pub could become a Tesco or a Sainsbury’s, or converted into luxury flats at a moment’s notice."
Save the Wheatsheaf campaigner Chris McQuiggin said: "If the council was really committed to protecting our pub in the long term, they have the power to do so.
"In light of the huge public support and the backing that this campaign has received, I don't know why the council are refusing to listen to local residents."