Heatherton Road will close so workers can remove railway tracks.
VicRoads issued an alert to motorists about ongoing works around the new Noble Park Railway Station precinct, which will include asphalting the road surface.
Heatherton Road will be closed at the train line in both directions from 6am on Wednesday 6 June until Monday 18 June.
Signed detours will be in place along Corrigan, Chandler, Kelvinside and Lightwood roads and Douglas Street.
VicRoads said delays were expected and advised motorists to avoid the area if possible.
Visit traffic.vicroads.vic.gov.au for real-time traffic information and allow extra travel time.
