The second use of the TOPS classification Class 21 for locomotives used on the British railway network came through the use of a number of related diesel-hydraulic and diesel-electric locomotives procured following the opening of the Channel Tunnel. The total of 16 locomotives were obtained by two separate operators, with some used for freight, and others to propel service trains and as "Thunderbird" locomotives.

In 2005, Euro Cargo Rail (ECR) was formed as a freight operator in France by English, Welsh and Scottish Railway (EWS). Its initial operations were carried out by a quartet of Vossloh G1206 diesel-hydraulic locomotives. Although these locomotives were intended for use in France, maintenance was planned to be carried out at EWS's depot at Dollands Moor, close to the Eurotunnel terminal at Cheriton. Because the locomotives would be operating on railways in Great Britain, they were allocated numbers in the TOPS system as Class 21. Two similar G1000 locomotives were procured in 2007.