It happened around 1pm on the westbound carriageway of the H3 Monks Way at the junction of Colley Hill in the Bradwell area.
The rider of the grey BMW motorcycle, a 51-year-old man, sustained serious injuries and was taken to hospital for treatment where he remains.
The driver of the silver Audi Q3 was not injured.
Investigating officer PC Phil McGlue, based at Milton Keynes police station, said: “I would like to appeal to anyone who saw this incident to come forward, especially if you have any dash cam footage which could relate to it.
“If you have any information which you think could be relevant, please call us on 101, quoting reference number 43220227625.”
> Alternatively call 999 if you have witnesses a car accident. Even if doesn't appear severe, the authorities should be notified. Let the 999 operator know the location and number of people involved.