On 23 May 1940, the Regiment landed at Cherbourg and moved up to the line of the Somme, which was at that time the limit of the German advance. The first task given to the Regiment, which was equipped with Mark VIBs, A9s and A13s, was that of co-operating with the French Army in a counter-attack on Abbeville. In the ensuing engagement, 'A' Squadron lost all but two of its tanks. Following this, the Regiment took part in a number of small defensive actions but, although one or two local successes were gained, the German weight of armour was such that the Anglo-French force was quickly pushed back. A composite squadron was formed by the 2nd and 5th Royal Tank Regiments and covered the 400 mile withdrawal to Cherbourg, while the main body of the Second left Brest by ship for England on 16 June 1940.
The Regiment was re-equipped with A13s and sailed for the Middle East in August when, on arrival in Egypt, it formed part of the 4th Armoured Brigade. The Regiment's first action in the Western Desert was at Hileigat and this was followed by the Battle of Sidi Barani and the capture of Bardia and Tobruk. The Regiment then took part in the attempt to cut off the Italian Forces withdrawing from Benghazi and after the battle of Beda Fomm 20,000 Italians were marched off to POW Camps.
Shortly after the entry of Japan into the war, the 7th Armoured Brigade was sent to assist the defence of Singapore, and in January 1942 the Regiment having been re-equipped with Stuart tanks embarked from Suez. The Second arrived in Rangoon on 21 February and, within 28 hours of arrival, one of the squadrons was in action 70 miles away from the city. The whole Burma campaign, in which the Regiment bore a large proportion of the fighting, was a successful rear guard action and withdrawal. On 19 April 1942 the Second came under the command of the Chinese Army for a few days and during the defence of Magwee Oilfields had several engagements. After 3 months continuous fighting the Regiment reached Kalewa on the river Chindwin with about 35 of its 50 tanks. As the tanks could not be ferried across, they had to be destroyed and the crews had then to march on foot over the mountains to Tamu. The Regiment then moved to Dhond where it was reinforced and re-equipped with Grant tanks.
In September 1942, the Second moved to Iraq and in May 1943 to Syria where it was re-equipped with Sherman tanks. Six months later the Regiment was again moved to Egypt and eventually embarked for Italy in April 1944 to come under command of the 5th Corps on the Adriatic Coast. With one brief interval, the Second remained in the forward area throughout the remainder of the summer and throughout the winter. In the last battle of the Italian Campaign in April 1945, the Second formed part of an exploiting force with 43 Ghurka Brigade and led the advance to Medicina and the River Reno. At the end of the war the Regiment was deployed north of the River Po and 'A' Squadron entered Austria on the night of VE Day.