The Western Freeway was closed in both directions between Bacchus Marsh and Ballan due to the pile-ups just before 4pm yesterday at Myrniong, about 58 kilometres west of Melbourne.
Police said two males were rushed to hospital in a critical condition, and one crash alone – which didn't result in any injuries – involved about 14 vehicles. Paramedics earlier said one patient was in a critical condition.
There were five other crashes nearby and 20 people were taken to various hospitals, police said, blaming heavy fog and motorists not driving to the conditions.
"Due to the reduced visibility in the area police are urging motorists to slow down, drive to the conditions and take note of any road safety signage in the area," police said, about 1am today.
Ambulance Victoria earlier said 20 patients were taken to hospital from the Myrniong crash, including one to Royal Melbourne Hospital in a critical condition.
The other 19 were taken in stable conditions to Royal Melbourne, Ballarat Base Hospital, Sunshine Hospital and Footscray Hospital, paramedics said.
The reason for the disparity in patient numbers was unclear.
Commuter chaos returning to Geelong
A truck driver died in a collision with a train in Geelong, halting V/Line services to the city from the capital, and the West Gate Freeway was shut outbound for almost an hour.
There were no suspected injuries, Victoria Police confirmed.
The West Gate Freeway began reopening by 5pm and traffic eventually cleared but V/Line services between Lara and Waurn Ponds were still cut early this morning.
The Western Freeway reopened just before 1am.
Earlier, motorists were being forced off the freeway at Bacchus Marsh or Ballan and made to detour all the way to Geelong to get through, according to Vic Roads.
"There are reports of extensive fog covering parts of the Western Freeway," a spokesperson said yesterday.
"Motorists should slow down, drive to the conditions and have their headlights on to be better seen."
Earlier yesterday, police closed all outbound lanes of the West Gate Freeway from Grieve Parade, Altona North, after a collision, but reopened two lanes about 5pm.
All drivers bound for Geelong were directed onto a single lane at the Grieve Parade exit, which caused delays of more than 90 minutes, stretching as far back as the Domain tunnel.
Truck driver killed in collision with train
The traffic chaos happened within hours of a fatal collision between a truck and a train in North Shore, near Geelong, which closed the train line for those travelling between Lara and Waurn Ponds.
About 25 passengers were evacuated from a V/Line train after it slammed into a truck, killing the truck driver on impact.
Major delays on the Geelong and Warrnambool lines continued into the night with emergency services still at the scene.
A spokesperson from V/Line said trains would continue to operate between Southern Cross and Lara, with coaches to transport passengers between Lara and Waurn Ponds.
The same arrangements were in place west of Geelong to Warrnambool.
A spokesperson said the lines would remain closed between Lara, on the Melbourne side of Geelong, and Waurn Ponds, on the Warrnambool side, until further notice.