The government has named a consortium led by German firm Siemens as its preferred bidder to build new train carriages for its Thameslink route.
Siemens beat competition from Bombardier, which runs the UK's last remaining train factory in Derby.
The £6bn North-South cross-London Thameslink programme will require 1,200 new carriages.
Siemens said it was delighted with the decision, while Bombardier said it was "extremely disappointed".
Transport Minister Theresa Villiers said in a statement that the Siemens-led venture represented the best value for money for taxpayers.
The first new train will be delivered by the start of 2015, with the order completed by the middle of 2017.
Siemens said the contract would lead to the creation of 2,000 jobs across the UK, including up to 300 at a factory in Hebburn, South Tyneside.
Siemens already employs about 16,000 people in the UK.
The contract to build carriages for the Thameslink upgrade is the second major bid Bombardier has lost to overseas competition.
In 2009, the company also lost out on a contract to build a fleet of inter-city "super express" trains to Japan's Hitachi.
It is a crucial time for Bombardier, which employs 3,000 people in Derby, as most current orders will soon be finished.
A company spokesman said: "We will need to be debriefed by the Department for Transport to understand why we were unsuccessful. Since the procurement process is still underway, and the contract has not been finalised, we cannot comment any further."
The Unite union said the news was a "hammer blow" for Derby and for British manufacturing.
"The government's decision to award this contract to a consortium which does not have British manufacturing and British job creation as its prime focus is absolutely disgraceful," said Mark Young, regional co-ordinating officer for Unite.
"The decision is a major blow for jobs in the East Midlands, not just at Bombardier but in the local supply chain, which has the largest concentration of train supply companies in the UK."
Rupert Brennan-Brown from the Derby and Derbyshire Rail Forum (DDRF), a group of 100 rail-related businesses in the Derby/Derbyshire area, also said it was disappointing news for Bombardier.
But he added: "There continue to be significant opportunities for the 100 members of the DDRF to supply products and services for both the Thameslink project generally and the new Siemens fleet for Thameslink."