Prosecutors allege Jack Aston was criminally negligent in failing to take heed of signs alerting drivers of a three-metre clearance ahead, as well as a warning sign on the bridge and a red flashing light triggered by a sensor on the road.

Mr Aston was driving the 3.6-metre-high bus for Gold Bus Ballarat on February 22, 2016, when he crashed into the bridge at 56km/h at 10.22am. The impact pushed the top part of the vehicle back to the fifth row of seats, the County Court heard on Tuesday.

Four women and two men, who were passengers while attending a conference at the Melbourne Convention and Exhibition Centre, suffered injuries including head and spinal fractures, broken collarbones and facial lacerations. Mr Aston was also seriously injured.

Mr Aston, 55, has pleaded not guilty to six counts of negligently causing serious injury.

Prosecutor Robert Barry, outlining his case to the jury, said signs dotted over the 290 metres before the bridge warned drivers of a low clearance, as did a sign on the bridge.

A sensor 81 metres before the bridge triggered the flashing light if it detected high vehicles. Mr Barry said the flashing light activated when the sensor detected the bus, while another motorist sounded a horn and flashed headlights when it became clear the bus was headed towards the bridge.

A sign on the bus dashboard said it was 3.8 metres high, the prosecutor said.

Mr Aston was based in Ballarat and had just picked up 14 passengers from the convention centre minutes before the crash, the court heard, having been allocated the job that morning.

The woman hosting the group told the driver they were running late in their trip to visit South Melbourne, St Kilda and Albert Park, but Mr Aston later told police he was not in a hurry as he drove, although he did not know the area.

"I was concentrating on driving, I suppose, looking at what's going on around me. I didn't see any signs," he told police about a fortnight after the crash.

Defence counsel Richard Edney called on the jurors to keep open minds and consider two critical issues: the long history of vehicle crashes into the bridge and the level of training and assistance Mr Aston received from his employer.

The driver rarely worked in Melbourne, Mr Edney said, and was "driving down a road he had never driven down before".

The prosecutor said the warning signs were all visible to motorists and the weather fine that morning. Police found no signs the bus braked before the crash.

The trial continues before judge Bill Stuart.