Stephen Samuel Wise was born in Budapest in the Austro-Hungarian Empire, the son and grandson of rabbis. He emigrated to New York as an infant with his family where his father became rabbi of Rodeph Sholom, a Manhattan Conservative congregation of wealthy German Jews.
Wise studied at the College of the City of New York, Columbia College (B.A. 1892), and Columbia University (Ph.D. 1901), and later pursued rabbinical studies under Richard Gottheil, Kohut, Gersoni, Joffe, and Margolis. In 1933, Wise received an L.H.D. from Bates College.
Rabbi Wise was an early supporter of Zionism. He was a founder of the New York Federation of Zionist Societies in 1897, which led in the formation of the national Federation of American Zionists (FAZ), a forerunner of the Zionist Organization of America. At the Second Zionist Congress (Basel, 1898), he was a delegate and secretary for the English language. Wise served as honorary secretary of FAZ, in close cooperation with Theodor Herzl until the latter's death in 1904.
Wise and others laid the groundwork for a democratically elected nationwide organization of 'ardently Zionist' Jews, 'to represent Jews as a group and not as individuals'. In 1918, following national elections, this Jewish community convened the first American Jewish Congress in Philadelphia's historic Independence Hall.
After the FAZ transformed into the Zionist Organization of America, Rabbi Wise fulfilled positions as both president and vice president during his lifetime.
Wise was a close friend of President Franklin Delano Roosevelt, who turned to Wise for advice on issues concerning the Jewish community in the United States. In addition, Wise had also acted a liaison to previous President Wilson.
In 1914 Wise co-founded the NAACP (National Association for the Advancement of Colored People). Other Jewish co-founders included Julius Rosenwald, Lillian Wald, and Rabbi Emil G. Hirsch.
In 1925, Wise became Chairperson of Keren Hayesod whilst he continued his efforts to bring the Reform movement around to a pro-Zionist stance. With the rise to power of the Hitler regime, Wise took the position that public opinion in the United States and elsewhere should be rallied against the Nazis. He, along with Leo Motzkin, encouraged the creation of the World Jewish Congress in order to create a broader representative body to fight Nazism. He used his influence with President Roosevelt both in this area as well as on the Zionist question.
In 1933, acting as honorary president of the American Jewish Congress, Wise led efforts for a boycott of Nazi Germany. He stated "The time for prudence and caution is past. We must speak up like men. How can we ask our Christian friends to lift their voices in protest against the wrongs suffered by Jews if we keep silent? What is happening in Germany today may happen tomorrow in any other land on earth unless it is challenged and rebuked. It is not the German Jews who are being attacked. It is the Jews".Urged by Wise to protest to the German government, U.S. Secretary of State Cordell Hull issued a mild statement to the American ambassador to Berlin complaining that "unfortunate incidents have indeed occurred and the whole world joins in regretting them."
Wise died on April 19, 1949, aged 75. He is interred in an unmarked mausoleum in Westchester Hills Cemetery in Hastings-on-Hudson, New York. The Stephen Wise Free Synagogue, which he founded in 1907 and served as Rabbi until his death, is named after him, as is Stephen S. Wise Temple in Los Angeles, which was founded by Rabbi Isaiah Zeldin in 1964.