The Rock Form sculpture, by Barbara Hepworth, went missing earlier this year after being removed ahead of the shopping centre's multi-million pound redevelopment.
It is said to be worth at least £1m.
Council leader Roger Lawrence has written to Chancellor George Osbourne asking him to step in and prevent the piece from being sold by property firm Delancy and owners Royal Bank of Scotland.
People behind the online petition, listed on the 38 Degrees campaign website, are aiming for 2,000 signatures.
The petition states: "This wonderful, iconic sculpture is a local landmark, and by far the best single piece of artwork in Wolverhampton.
"Plans for the redevelopment of the Mander Centre must be modified to include the Hepworth and it must be returned to its place of pride as soon as practicable, and a firm guarantee given of this."
A similar piece recently sold for £5m.