London Northwestern Railway's hourly service will operate from Birmingham New Street.
After a phased launch, which will see the route run initially to Crewe, the full rollout next May will eliminate the need for passengers heading to MAN to change in Crewe, Wilmslow or via Manchester city centre.
LNR's Managing Director Denise Wetton said the route would be the first direct service between MAN and the West Midlands "for decades".
Chris Woodroofe, MAN's Managing Director, added the route could be particularly useful to long-haul travellers "who might currently fly indirectly from other airports, or face a long journey to the South East".
Services will complement LNR and Avanti West Coast's existing services from London to Birmingham New Street, opening up single-change journeys between London and Manchester airport.
The route will call at Tame Bridge Parkway, Darlaston, Willenhall, Wolverhampton, Stafford, Stone, Stoke-on-Trent, Longport, Kidsgrove, Alsager, Crewe, Sandbach, Holmes Chapel, Wilmslow, Styal and Manchester airport.