The Ethiopian Airlines service launches on December 1 and will be operated four times a week on board a Boeing 787.
The airline’s chief executive Tewolde Gebremariam said passengers taking the flight, which lands in the Ethiopian capital at 6am, will then be well placed to take advantage of the airlines many onwards connections.
He added: "It will be the only and first direct flight from Manchester to the heart of Africa and with connecting flights."
Gebremariam said the flight would save people living in the north of the UK from having to travel to London to catch a flight.
He added while it was expected to be most popular with the VFR market, it should appeal to both leisure and business travellers too.
"It’ll be a very good opportunity for them to travel direct from Manchester to wherever their business is in Africa," he said.
Gebremariam added a plan to market the route with Manchester airport and local government should also make it popular.
He added travellers using the flight will not only benefit from the African connections available but can also choose to continue their journey to any of the 110 global destinations available.
This list is growing too, Gebremariam said, with Chicago, Geneva and Barcelona connecting in June, Jakarta being added in July and Istanbul and Moscow in September.
He added agents would also be able to book commissionable packages with the airline’s tour operator ET Holidays once it launches in June or July 2018.