Sir Richard Branson has lost the battle to continue running the West Coast Main Line that his Virgin Rail company has been operating since 1997.
Giant transport company FirstGroup will take over a new 13-year franchise.
FirstGroup, which already has a number of rail franchises including Great Western and ScotRail, will start operating the London to Scotland West Coast line in December.
During Virgin's 15 years of operating the line, tilting, high-speed Pendolino trains began serving cities from Birmingham and Manchester to Liverpool and Glasgow.
Around 31 million passengers use the West Coast services every year.
Announcing the new franchise winner, Rail Minister Theresa Villiers said it would deliver "big improvements for passengers, with more seats and plans for more services".
But the RMT union warned of "massive cuts to jobs and passenger services and huge increases in fares".