Police allege Brett Michael Russell, 60, was driving a truck that collided with a bus carrying students from Loreto College, Ballarat on the Western Highway on September 21.
The students were en-route to Melbourne Airport ahead of a NASA Space Camp in the United States.
The impact of the crash caused the bus to roll down an embankment at Pentland Hills, near Bacchus Marsh.
Emergency services took 33 people to hospital after the crash.
Mr Russell faced Melbourne Magistrates Court on Monday afternoon charged with 46 offences including reckless conduct causing serious injury, dangerous driving causing serious injury, and reckless conduct endangering life.
