Born on February 4, 1884, in South Bethlehem, Pennsylvania, John Nevin Sayre grew up with his two parents and his brother, Francis Sayre. His father, Robert Sayre, was the general manager of the Bethlehem Iron Works and founder of the Sayre Mining and Manufacturing Company, making Sayre's family quite fortunate. His mother, Martha Nevin, was the daughter of the founder of Franklin and Marshall College. Sayre attended boarding school and summer camps with his brother during their childhood, displaying the boys' privileged lifestyles. Sayre graduated with a Bachelor of Arts from Princeton University in 1907. Following his schooling at Princeton, he received his Bachelor of Divinity from Episcopal Theological School in 1911. In addition, the ambitious Sayre attended Union Theological Seminary from 1908-1910 and also attended University of Marburg in Germany from 1913-1914.

Following and during his extensive educational experiences, he was an instructor at two separate universities: Princeton University from 1911-1912 and 1914-1915 and Boone University in Wuchang, China, in 1913. After teaching, his heart led him to become a minister. He served as a minister at Christ Church in Suffern, New York, from 1915-1919, during World War I. His church community was not completely supportive of his position on pacifism, so after the war ended he felt his calling was to preach his word to other parishes and to the youth of the community. It was then that Sayre was to become one of the co-founders of Brookwood Labor College, which was conceived by a group from the Fellowship of Reconciliation (FOR). Sayre became a teacher at Brookwood from 1919-1921 until he began his career as a peace activist, primarily working through FOR to serve other organizations and countries.

Sayre was known by his close friends and family as a quiet man with an eclectic sense of humor. By joining the FOR in 1921, Sayre became well-known as one of the primary peace activists of his time. One of his first active strides toward peace was made when he visited Germany in January of 1921, working with an international reconciliation group. He traveled throughout the country speaking in 15 separate urban areas while observing post-war conditions. He became the editor of The World Tomorrow from 1922-1924 and worked as associate secretary from 1924-1935, getting his name out into the American community through the FOR. He was also the co-editor of Fellowship magazine for many years. In 1927, in one of Sayre's more notable efforts toward peace, he traveled to Nicaragua, traveling over mountains by horseback to encourage peace deals with the United States. His goal was to reach guerrilla leader Augusto Sandino, but in failing to do so, he managed to stop the bombing of innocent Nicaraguan villages and the war by appealing to the United States senators and the State Department to support his message.

Between the years of 1935-1950, Sayre was a very busy man. He often found himself the head, the president, or the chair of various types of groups, such as the Fellowship of Reconciliation, the National Peace Conference, and the Emergency Peace Campaign. Following World War II, Sayre found himself rushing to the aid of European war resisters, which included pastors, Jews, and several others who were imprisoned or even tortured. After becoming the international secretary of the FOR, Sayre began traveling several different regions. In 1947 alone, he visited 15 Latin American nations, covering upwards of 14,000 miles. During his travels he was able to make some significant changes for the island nation of the Philippines. He was able to convince the president, Elpidio Quirino, to commute the death sentences of more than 100 Japanese prisoners of war by permitting them to return home to Japan. In the following years, Sayre continued to free Japanese prisoners from other nations.

Sayre continued to stay active throughout his 60s by climbing mountains and walking for many miles. He even marched for five miles in a demonstration against the war in Vietnam at the age of 82. His clearly active lifestyle was brought to an abrupt stop in 1967 when he suffered a stroke. He spent most of his later life in Rockland County, New York. On September 13, 1977, Sayre died in his home in South Nyack, New York, at the age of 93. Two years after his death, the Episcopal Peace Fellowship established the John Nevin Sayre Award to be given to someone every three years for their commitment to justice and peace.