The first flight after a 21-month hiatus is due to depart on 15 December from terminal two and the airline will run a three-times weekly service on the Boeing-787 Dreamliner.
The Saudi Arabian flag carrier began operating the Manchester-Jeddah route in 2014. According to the airport, more than 97,000 passengers used the service in 2019.
Manchester airport managing director, Karen Smart, said the return of the airline is "wonderful news" and demonstrates the "renewed confidence amongst passengers and airlines as we begin to emerge from the pandemic".
"This is a route that is hugely important to communities across the north, given it is the only direct service to Saudi Arabia outside London," she added.
"It also has substantial economic benefits for our region, given the ever-growing trade and investment partnership between the UK and Saudi Arabia."
