The fear of a possible nuclear war was never far from President Kennedy's mind. During the presidential campaign, Candidate Kennedy wrote a private letter to President Eisenhower expressing concern that the campaign might disturb the negotiations for a Test Ban Treaty. Kennedy expressed his support for any agreement that Eisenhower might reach. Once he was in office, President Kennedy made reaching a Nuclear Test Ban Agreement a priority. He was hoping to advance the negotiations at his summit meeting with Khrushchev in Vienna. Khrushchev, however, was not interested in reaching any agreement, since he believed it was in the Soviet Union's interest to continue nuclear testing. Kennedy was totally unsuccessful in convincing Khrushchev otherwise.

Kennedy continued to search for ways to kick-start the negotiations for a US-Soviet Nuclear Test Ban Treaty. When Kennedy assumed the Presidency, an unofficial mutual US-Soviet moratorium on nuclear testing had been in effect. But in the fall of 1962, the Soviets resumed testing. By November, the Soviets had conducted 50 atmospheric tests in 60 days, including the explosion of a 50€“megaton bomb. Kennedy felt compelled to order the US to prepare for its own resumption of nuclear testing, but he remained reluctant to restart testing. In a January 1962 press conference, when asked to cite the most disappointing thing of his first year in office, Kennedy named his failure to reach an agreement on a nuclear test ban. Kennedy ordered the renewed tests to take place in the Pacific, and not at the previous testing site in Nevada.

Kennedy's reluctance to go ahead with nuclear testing was palpable. He believed it necessary to speak directly to the American people and delivered a 45-minute televised address regarding the need to resume testing. After going though all of the scientific and technical reasons above ground testing was necessary, given that the Soviets had failed agree to a mutual ban. Kennedy said: €œNevertheless, I find it deeply regrettable that any radioactive material must be added to the atmosphere€“ that even one additional individual's health may be risked in the foreseeable future. And however remote and infinitesimal those hazards may be, I still exceedingly regret the necessity of balancing these hazards against the hazards to hundreds of millions of lives which would be created by any relative decline in our nuclear strength. "

Kennedy made one last attempt to reach out to the Soviets to achieve an agreement with them before the US resumed testing. But any possible agreement was doomed by American demands that on-site inspections take place, a demand the Soviets rejected. Some progress was made in September, when the Soviets agreed to a non-binding ban on atmospheric testing and a moratorium on underground testing, while rejecting a comprehensive ban. The US rejected that proposal believing that only a comprehensive treaty would work.

For the next six months, messages went back and forth between the Soviets and the Kennedy Administration. From the Soviets, the message always seemed contradictory. On one hand, Khruschev continued to indicate his interest in reaching an agreement. On the other, he kept placing obstacles in the path of reaching that agreement.

To break the logjam Kennedy decided to give a major speech to send a message to the Soviets. He used a commencement address at American University to reach out to the Soviets and said: €œNo government or social system is so evil that its people must be considered as lacking in virtue. As Americans, we find communism profoundly repugnant as a negation of personal freedom and dignity. But we can still hail the Russian people for their many achievements--in science and space, in economic and industrial growth, in culture and in acts of courage"

President Kennedy announced a unilateral cessation of American nuclear testing, followed by an announcement of a resumption of talks with the Soviets. The speech was hardly noticed in the United States. The Soviets, however, reacted warmly to the speech, publishing its full content in Soviet newspapers. In addition, the Soviets allowed the Voice of America to broadcast Kennedy's remarks, ceasing the routine jamming of VOA broadcasts. Kennedy used the prestige he had gained as a result of his handling of the Cuban Missile Crisis, in a bold bid to reset US-Soviet relations to avoid what many had believed was an unavoidable war.

On June 20, the first step was achieved when the United States and the Soviet Union reached an agreement to install a so-called "Hot Line" connecting the Oval Office and the Kremlin telephonically. Negotiations continued. The combination of Kennedy's high public approval rating and Khrushchev's anxiety over growing Chinese power led to an agreement. On July 25th 1963, the treaty was signed outlawing atmospheric, underwater and space testing. The treaty did provide for continued underground testing.

Kennedy was worried about achieving Senate approval for the agreement, so he addressed the nation in a televised speech regarding the treaty. The Senate approved the treaty, by a vote of 80 to 19; it was the first of what would be a long line of treaties between the US the Soviet Union that limited the development of nuclear weapons.