The Frankston-Dandenong Road bridge in Dandenong South is expected to be closed for reinforcing works until 30 May.
Major Road Projects Victoria said the road between Princes Highway and Kirkham Road will be closed in both directions during the 24/7 works.
The bridge was built in the 1950s and carries 31,000 vehicles a day.
Traffic detours are via South Gippsland Highway, Greens Road and Dandenong Bypass.
