The two-vehicle collision happened on the Foreglen Road between Claudy and Dungiven at about 06:30 GMT on Monday.
Police said a car and a van were involved in the collision.
Three other people were treated at Altnagelvin Hospital for minor injuries and have since been discharged.
Police appealed for anyone who was travelling on the Foreglen Road at the time of the accident to contact them.
Sinn FÃ©in MLA Caoimhe Archibald said her thoughts were with the dead man's family.
"I would like to express my sympathies to the family and friends of the man who has died as a result of this morning's crash," she said.
"This is the second death on the A6 in weeks and, as we enter into the winter months, I would urge all road users to exercise care and caution on the roads at all times and to allow for extra travelling time if conditions are poor."
Last month, Loreto Douglas,  64, a child care worker from Derry died after a three-vehicle crash on a stretch of the A6 at the Glenshane Pass.
The man who died following a serious road traffic collision on the main Londonderry to Belfast road was Ryan McCaul, 31, from Dungiven.