As Commander-in-Chief, Cunningham’s main concern was for the safety of convoys heading for Egypt and that of Malta, whose significance he fully appreciated, and conducted an aggressive policy against the Italian Fleet, with victories at Calabria, Taranto and Cape Matapan. He was also able to provide valuable support to ground operations, especially in both the campaigns in Greece and Crete where the Royal Navy evacuated thousands of Allied troops against powerful opposition from the Luftwaffe. On 21 October 1943 he became First Sea Lord of the Admiralty after the death of Dudley Pound and Chief of the Naval Staff until 1945. He also served under General Dwight D Eisenhower, the Supreme Commander, Allied Expeditionary Force and commanded the large fleet that covered the Anglo-American landings in North Africa (Operation Torch in November 1942) and then the naval forces used in the joint Anglo-American amphibious invasions of Sicily (Operation Husky in July 1943) and Italy (Operation Baytown and Operation Avalanche in September 1943).
Cunningham had been made a Knight Commander of the Bath in 1939. In 1945 he was made a Knight of the Thistle and was elevated to the House of Lords as Baron Cunningham of Hyndhope, Kirkhope, county of Selkirk. In 1946 he was made a Viscount and admitted to the Order of Merit. He acted as Lord High Steward during the coronation of Queen Elizabeth II in 1953 and was Lord High Commissioner to the General Assembly of the Church of Scotland. He died suddenly in London on 12 June 1963 after attending a meeting at the Admiralty. He was buried at sea off the Nab Tower, Portsmouth from HMS Hampshire. Highly regarded by both contemporaries and subordinates, General Dwight D Eisenhower said of him in his diary:
"Admiral Sir Andrew Browne Cunningham. He remains in my opinion at the top of my subordinates in absolute selflessness, energy, devotion to duty, knowledge of his task, and in understanding of the requirements of allied operations. My opinions as to his superior qualifications have never wavered for a second."