Starting from, the Thames–Clyde Express travelled by the former Midland Railway's main line through Leicester, sometimes with reversals when serving Derby and Nottingham, as far as Leeds. After another reversal there, the train crossed the Pennines to the scenic Settle-Carlisle route, still on former Midland Railway territory. Crossing into Scotland, the train used the former Glasgow and South Western Railway's Glasgow South Western Line into Glasgow St Enoch, the city's G&SWR terminus. The train could not compete for London-to-Scotland traffic with the faster trains travelling on the West Coast Main Line. Its route was longer and steeper, and Midland expresses could not ignore major population centres en route, especially Leicester, Sheffield and Leeds. In Scotland, it took a longer route in order to provide a service to Dumfries and Kilmarnock. As a result, few travellers after the 1920s travelled the full length of the route. The Thames–Clyde lost its title at the outbreak of World War II, in common with almost all named trains in the UK. However, the title was restored in September 1949 as part of the post-war return to normality. The effect of regional division, mining subsidence along part of the route between and, and underpowered locomotives meant that its performance was actually inferior in time to that achieved in 1939. In 1962, the Thames–Clyde took eight hours and 50 minutes for the complete journey, leaving London at 10.15, and then calling first at Leicester London Road at 11.52. Further stops were made at Trent and Chesterfield, before reaching at 13.19 and Leeds City at 14.25 - so this latter stage of 39 miles took over an hour as a result of subsidence-induced speed restrictions. From there, the train ran non-stop to Carlisle. Three more stops were made at,, and before reaching Glasgow, St Enoch at 19.05. The rival Royal Scot on the West Coast route stopped only twice and took seven hours, twenty minutes. However, the Thames–Clyde provided a useful service from the East Midlands and Yorkshire to Scotland.
In 1964, The Waverley ceased to run during the winter, and so additional coaches for Edinburgh were carried on the Thames–Clyde. But the train then made additional stops on the Settle & Carlisle line which were otherwise served by The Waverley: Skipton, Hellifield, and Appleby West railway station. The 1966 closure of St Enoch resulted in the transfer of the service to. In 1968, a further delay was added by a stop at Nottingham, which meant a reversal. In 1970, a short-lived Sunday diversion to Derby brought another reversal, although this had ceased by 1973. The train had acquired a bad reputation for slowness and unpunctuality.
Cessation of services
The train lost its title in May 1974 when the West Coast Main Line was electrified to Glasgow, but the service continued to run until 1976.
