The Class 45 and 46s were pretty much identical to the 44s, also weighing in at around 135 tonnes and powered by a diesel power unit produced by Swiss engineering company Sulzer. However, the newer power units produced 2500 horsepower, 200 more than their predecessors.

This led to BR placing a more substantial order of 127 locos for Class 45s, this was so many in fact, that Crewe Works were also drafted in to assist Derby with their construction. The first BR Class 45 entered service in late 1960, with the class soon becoming the main loco to work out of St Pancras on the Midland mainline services, demoting the dwindling number of steam locos to cover local services or freight. The 45s were intended to be allocated to multiple regions during their construction and this was initially the case with locomotives allocated to London Midland and Western Region sheds as well as other regions for short stints of training. They soon settle down to more regular work on Midland mainline and Western Region services.

With the introduction of the HSTs on the Midland and Cross Country routes, as well as the introduction of Class 56s to coal traffic, the 45s were moved to the Trans-Pennine route to work passenger services across the North of the country.