Blackstone was born in Adams, New York and became an evangelical Christian when he was 11 during revival meetings at a local Methodist church. He enlisted for military service during the American Civil War but was not accepted due to "frailness of body". Instead he joined the United States Christian Commission (similar to the modern Red Cross) and was stationed much of the time at General Ulysses S. Grant's headquarters as coordinator of medical services for injured combatants.
On June 5 1866, Blackstone married Sarah Lee Smith and settled in Oak Park, Illinois in 1870, where he engaged in the "business of building and property investments". Under the influence of evangelical preacher Dwight Lyman Moody he turned to religion, and in his preaching as well as in his writing, he proclaimed the premillennial return and rapture of the Church. As he ministered across the U.S., Blackstone spoke with increasing fervor in support of Zionism.
In 1881, he wrote, Jesus is Coming.
On November 24-25, 1890, Blackstone organized the Conference on the Past, Present and Future of Israel at the First Methodist Episcopal Church in Chicago where participants included leaders of both Jewish and Christian communities. Resolutions of sympathy for the oppressed Jews living in Russia were passed, but Blackstone was convinced that such resolutions - even though passed by prominent men - were insufficient. He advocated strongly for the resettlement of Jewish people in Palestine. Accordingly, the Blackstone Memorial of 1891 was drafted as a petition signed by 413 prominent Christian and Jewish leaders in the United States.
It read, in part: : “Why shall not the powers which under the treaty of Berlin, in 1878, gave Bulgaria to the Bulgarians and Servia to the Servians now give Palestine back to the Jews?…These provinces, as well as Romania, Montenegro, and Greece, were wrested from the Turks and given to their natural owners. Does not Palestine as rightfully belong to the Jews?”
Also in 1891, Dr. W.E. Blackstone stated that since the general “law of dereliction” did not apply to the Jews in regards to Palestine: “for they never abandoned the land. They made no treaty; they did not even surrender. They simply succumbed, after the most desperate conflict, to the overwhelming power of the Romans...”
Although he initially focused on the return of Jews to the Holy Land as a prelude to their conversion to Christianity, out of a pious wish to hasten the coming of the Messiah. He increasingly became concerned with the deadly, Russian, government-instigated pogroms and believed that it was necessary to create a Jewish homeland in Palestine. He was, furthermore, persuaded that neither the European nations nor the United States would accept as many Jews as needed to escape from Europe.
Blackstone and his daughter traveled to the Holy Land in 1888. He returned convinced that a return of the Jewish people to its ancient homeland was the only possible solution to the persecution Jews suffered elsewhere. He organized a “Conference on the Past, Present and Future of Israel” held on November 24-25, 1890. Christian and Jewish leaders attended, albeit not leaders of the Reform movement. The conference issued the Blackstone Memorial urging the great powers, including the Ottoman Empire, to return Palestine to the Jews.
In 1904, he began teaching that the world has already been evangelized, citing Acts 2:5, 8:4, Mark 16:20 and Colossians 1:23.