The Prince of Wales Bridge is closed in both directions after a lorry drove down the embankment and onto land alongside the M4 Westbound.
The lorry is believed to have hit the central reservation and then ended up off the road.
Gwent Police are at the scene and are advising motorist to avoid the area due to the heavy traffic.
The M4 westbound road is closed and police say they expect it will be closed all day and into the evening.
Traffic is being diverted on to the M48 where traffic is will be heavier than usual.
An Air Ambulance is on the scene and South Western Ambulance Service has confirmed that one male casualty has been taken to hospital by air ambulance. Their condition is not yet known.
Gwent Police are appealing for anyone who saw what happened to get in touch with them.
Highways England, which operates the bridge, has warned people to expect long delays.