In 1926 Winston Churchill, the Chancellor of the Exchequer, appointed Boothby as his parliamentary private secretary, a post he held for three years.

Boothby was a frequent visitor to Germany and in 1932 met Adolf Hitler. He was later to record that "I talked with Hitler for over an hour; and it was not long before I detected the unmistakable glint of madness in his eyes." Boothby came out of the meeting convinced that Hitler posed a serious threat to Britain's security.

In October 1933 Boothby made a speech where he warned: "If those of us who believe in freedom refuse to fight for our faith under any circumstances, then assuredly we will succumb to the military forces of Fascism or Communism, and most of the things which seem to make life worth living will be swept away."

Boothby joined a small group in the Conservative Party, including Winston Churchill and Leo Amery, that called for the government to increase spending on defence. In one speech Boothby suggested that the British government was in danger of betraying those soldiers who had been killed during the First World War. "In relation to the facts of the present situation our Air Force is pitifully inadequate. If we are strong and resolute, and if we pursue a wise and constructive foreign policy, we can still save the world from war. But if we simply drift along, never taking the lead, and exposing the heart of our Empire to an attack which might pulverize it in a few hours, then everything that makes life worth living will be swept away, and then indeed we shall have finally broken faith with those who lie dead in the fields of Flanders."

In January 1938 Boothby became the first person in public life to demand the introduction of compulsory national service. He followed this with a campaign to persuade Neville Chamberlain and his Conservative government to increase the frontline strength of the Royal Air Force from 1700 to 3500. However, both these suggestions were rejected by Chamberlain.

Boothby returned to office in 1940 when Winston Churchill appointed him as Parliamentary Private Secretary to the Ministry of Food. Boothby worked under Lord Woolton and was given responsibility for devising the National Milk Scheme, which provided milk for children and nursing mothers during the Second World War.

In 1941 Boothby was forced to resign after a Select Committee published a critical report of his behaviour before the war. The committee pointed out that Boothby had made a speech where he advocated the distribution of seized Czechoslovakian assets to Czech citizens living in Britain. It was claimed that this broke the rules of the House of Commons as Boothby had not disclosed that he had a financial interest in this policy.

After resigning from office Boothby joined the Royal Air Force. After completing his training as a pilot officer he became Adjutant of Number 9 Bomber Squadron at Honington with the rank of Flight Lieutenant.

In 1948 Boothby became an original member of the Council of United Europe and was a British delegate to its consultative assembly (1949-54).

Boothby was knighted in 1953 and raised to the peerage in 1958. He was also Rector of the University of St Andrews (1958-61) and Chairman of the Royal Philharmonic Orchestra (1961-63).