In September of 1888 he began a service of twenty-seven years as national secretary of the Intercollegiate Y.M.C.A. of the U.S.A. and Canada, a position requiring visits to colleges to address students concerning Christian activities.
From 1915 to 1928, Mott was general-secretary of the International Committee of the Y.M.C.A. and from 1926 to 1937 president of the Y.M.C.A.'s World Committee. During World War I, when the Y.M.C.A. offered its services to President Wilson, Mott became general secretary of the National War Work Council, receiving the Distinguished Service Medal for his work. For the Y.M.C.A. he kept up international contacts as circumstances allowed and helped to conduct relief work for prisoners of war in various countries. He had already declined President Wilson's offer of the ambassadorship to China, but he served in 1916 as a member of the Mexican Commission, and in 1917 as a member of the Special Diplomatic Mission to Russia.
The sum of Mott's work makes an impressive record: he wrote sixteen books in his chosen field; crossed the Atlantic over one hundred times and the Pacific fourteen times, averaging thirty-four days on the ocean per year for fifty years; delivered thousands of speeches; chaired innumerable conferences, and received dozens of awards. At 81, the Nobel committee awarded him one of the highest honors given on earth - the Nobel Peace Prize. He died at his home in Orlando, Florida at the age of eighty-nine.