According to South Korean maritime police and port officials, the North Korea-registered freighter Kangsong with a crew of 27 is en route from the North's western port of Nampo.
“The ship is expected to reach South Korean waters late Friday,” a South Korean unification ministry official told AFP new agency.
The landmark voyage is part of efforts to open a regular service involving South and North Korean cargo ships, but the two governments have yet to endorse the plan, he said.
According to the South Korean maritime police and port officials, the route is planned as a regular service linking Busan and Najin in North Korea.
The ship will make three round trips between Busan and Najin every month beginning Monday when it is scheduled to leave Busan port with 50 empty containers.
Kukbo Express Co, a South Korean company that runs the ship, said it opened the regular service expecting a steady growth in the volume of trade between the two Koreas.
The two Koreas have remained technically at war since the 1950-53 Korean War ended without a peace treaty, but economic exchanges have been growing in recent years.
Reports this week said Russia and China had both been eying the North Korea port of Najin as a potential shipping hub