The road now back open. Drivers were advised to avoid the route towards Bicester after the road was closed in both directions between the Miller & Carter roundabout and the HS2 roundabout.
The closure led to diversions through Berryfields and Quarrendon, with some motorists reporting delays of around 25 minutes.
Oxford Road was bumper to bumper, heading out of Aylesbury and Fairford Leys was busier than usual.
Posting on the Aylesbury Community Facebook page, residents shared updates from the scene, with one driver saying police were in attendance and traffic was being redirected away from the affected stretch of road.
Witnesses reported that those involved in the crash appeared to have escaped serious injury. One local resident who was at the scene said: "Everyone was okay-ish, thank God."
There has been no official information yet on the number of vehicles involved or the cause of the collision.
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