A man and a woman were taken to hospital after the crash, which happened just before 02:00 BST and saw a car hit the central barrier.
Essex Police said the woman, who was driving, suffered "serious injuries".
Clockwise queues on the Essex side of the crossing are back to junction 29 for the A127, and traffic is being diverted through the Dartford tunnel.
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Highways England said a 27m (89ft) stretch of barrier had been damaged by the crash, and an expansion joint on the bridge had also been affected.
Police have said drivers should expect delays and "seek alternative routes where possible".
Drivers are being warned of severe delays around the M25 after a crash caused the closure of the QE2 bridge.