The helicopter was primary used for transport during amphibious assault operations. Other opportunities are:

- combat support during evacuation operations and other maritime special operations
- on the water for search and rescue missions
- support for mobile forward refueling and re-armoring
- airmedical evacuation of accidents on the battle field with medical equipment.
The helicopter can carry 12 till 18 fully equipped Marines.

The CH-46E Sea Knight helicopters will be replaced by the new MV-22 Osprey. The last Sea Knights were withdrawn from operational service in 2013.

US Navy & USMC CH-46 Sea Knight