The base opened on 20 August 1943 as a Bomber Command Station and is situated not far from RAF Coningsby.

Stationed at East Kirkby were: No. 57 Squadron RAF, 27 August 1943 - 25 November 1943 .No. 630 Squadron RAF, 15 November 1943 - 18 July 1945. RAF East Kirkby served also as the headquarters of No 5/5 (Bomber) Group RAF in command of satellite stations at RAF Strubby, RAF Spilsby, RAF Hemswell and RAF Manby.

On 17 April 1945, near the end of the Second World War, a 57 Squadron Lancaster was being loaded with bombs when a fully armed 1,000 lb bomb was unintentionally dropped onto the tarmac. Because the bomb had had its fuse inserted it detonated, setting off the rest of the Lancaster's bombload. A massive explosion killed three airmen, injured 16 others, wrote off six other Lancasters beyond repair and badly damaged a nearby aircraft hangar.The final wartime raid from East Kirkby was flown on 25 April 1945. In total, 212 operations were carried out during the war, from which 121 Lancasters did not return. Another 29 aircraft were lost due to operational crashes or accidents.