Shepparton police Sergeant Rocky Fazzolari said the scooter rider had been riding west on High St, and was crossing the road at the Hoskin St intersection to the footpath on the other side when the crash occurred about 6pm on Monday, February 24.
A car, driven by a 26-year-old woman from the Shepparton area, was being driven west on High St and was turning left into Hoskin St, when it and the scooter collided, Sgt Fazzolari said.
The 52-year-old man riding the scooter was thrown on to the bonnet of the car and on to the windscreen.
The scooter rider, who was new to the Shepparton area, was not wearing a helmet.
The man was taken to Goulburn Valley Health by ambulance with a head injury and a laceration to the leg.
His condition deteriorated overnight and he was transferred to the Royal Melbourne Hospital the following day, where he remained in a serious condition on Wednesday, Sgt Fazzolari said.
A 28-year-old man who was a passenger in the car was also taken to GV Health after getting shards of glass in his eyes.
The woman who was driving the car, and a child who was a passenger, were not physically injured.
Police investigations into the crash are continuing.