The road was closed after the incident on the A4080 in Llanfaelog just after 10:00 GMT on Friday, and remains shut.
The man who was riding the motorbike has been taken to Ysbyty Gwynedd in Bangor. No one else was injured.
Officers want to speak to the drivers or passengers or two cars which were in the area at the time as they may have information about the crash.
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A motorcyclist has been taken to hospital with life-threatening injuries after a crash on Anglesey.