The crash near Stonehaven on Wednesday morning closed a highway west of Geelong in Victoria's south.
Deputy Prime Minister Richard Marles said the incident will affect many in the tight-knit Geelong community.
"My heart breaks hearing the devastating news of a school bus incident and death of a student in my hometown of Geelong," Mr Marles said on social media.
Authorities are yet to officially confirm any deaths.
Victorian regional healthcare provider Barwon Health said 13 people were being treated at Geelong University Hospital, 12 of them children.
Two people are in a serious condition, with one being transferred to Melbourne's Royal Children's Hospital.
Victoria Police said a school bus had rolled.
"It's understood several people have been seriously injured," a spokesperson said in a statement.
Victoria's Transport department reported the Hamilton Highway closed in both directions between Burnside Road and Friend-In-Hand Road "due to a serious collision".
"The closure is under the control of Victoria Police."
8°C