Three of the four citybound lanes are closed on the West Gate Freeway at Williamstown Road following a collision.
Delays are significant, with queues back to the M80 Ring Road interchange, the Department of Transport said.
Motorists are encouraged to use Geelong Road to avoid hold-ups.
The department has also reminded motorists that the Princes Freeway inbound exit ramp to Geelong Road is currently closed for West Gate Tunnel works. Motorists will need to use the M80 Ring Road and exit at Boundary Road, then use Little Boundary Road to Geelong Road.
Emergency services are on site, all lanes will open as soon as it is safe to do so.
Real-time traffic conditions are available at traffic.vicroads.vic.gov.au or via the VicTraffic mobile app.