In June 1940, as part of General Wavell's plan to confuse the Italians, the First went into action in a number of small raids across the frontier in the area of Fort Capuzzo. Following the Italians' invasion of Egypt, the first, still serving in the 7th Armoured Division and equipped with A9s as well as light tanks, took part in the successful advance on Sidi Barrani and the resultant full scale attack on Tobruk, Derna and Nechile. The Regiment was also involved in the attempted break-out by the Italian Forces at Beda Fomm and this action, which lasted for 24 hours, resulted in the capture of 20,000 Italian soldiers and 112 tanks. After these actions, the First returned to Cairo to re-equip with Matildas, A10s and A13s.
In April 1941, the Regiment was part of the Tobruk Garrison during its siege by the German Afrika Corps and was the only Regiment, of armour or infantry, to remain in the garrison for the entire period. In December, the Regiment was withdrawn to Alexandria, and moved to Mena in March 1942 having been re-equipped with Grant and Stuart tanks. In June 1942, as part of the 4th Armoured Brigade, the Regiment fought in the Battle of the Cauldron, and on 10 June, whilst acting as a flank guard, suffered heavy casualties. The battles at Knightsbridge and Gazala had been lost and with them most of the British tank strength. The Regiment was withdrawn to Mersa Natruh and hurriedly re-equipped with Honey and Lee tanks, in time to take their place in the Alamein Line. Furious fighting took place along the Line and the Regiment was fully committed, again losing a great many of its tanks. On 23 October 1942, the Regiment took part in the Battle of Alamein and the resultant exploitation to the Mareth Line. In May 1943, following the capture of Sfax, the First together with the 11th Hussars and the Fifth led the 7th Armoured Division into Tunis.
The Regiment took part in the Allied landings at Salerno and was involved in a series of actions around Mount Vesuvius. Early in 1944, the Regiment returned to England to prepare for the 'Second Front'. On 7 June 1944, it landed at Arromanches and was fully committed in the battles for Verriers and Tilly in the Bocage area of Normandy. In August, the First, in particular C Squadron, was instrumental in capturing Lisieux during the Falaise Pocket engagement and, subsequently, the Regiment was in the van of the advance to the River Seine.
From October to December 1944, the Regiment, as part of the 7th Armoured Division, took part in the capture of Undenhaut, Oosterhaut and the River Meuse. It was whilst defending the line of the River Meuse that two squadrons of the Regiment dismounted and acted as infantry.
Following the defeat of the German offensive in the Ardennes, the Regiment was engaged until February 1945 in clearing the Maas-Roer triangle and was again employed in the breakout from the River Rhine bridgehead during March. Then the Regiment moved eastwards, crossed the River Weser at Nienburg and advanced to Hamburg. There was continual resistance, but advances of 40 to 50 miles in a day were common. The First halted outside Harburg, a suburb of Hamburg, but an attack on the city was not necessary as it surrendered just before the German Armies capitulated.