Charles Netter established the school in 1870 on a tract of land southeast of Tel Aviv leased from the Turkish Sultan, who allocated 750 acres (3.0 km2) to his project. Netter, the first headmaster, introduced new methods of agricultural training. Baron Edmond James de Rothschild contributed to the upkeep of the school.
The name is taken from two passages in the Book of Jeremiah - Jeremiah 14:8 and 17:13. It was proposed by Wolf Grinstein, one of the school's first students, who later taught there.
In 1898, Theodor Herzl met Kaiser Wilhelm II at the main entrance of Mikve Israel during Herzl's sole visit to Eretz Israel. The meeting, a P.R. event engineered by Herzl to publically meet the Kaiser, was misinterpreted by the world media as a legitimization of Herzl and Zionism by Germany.  Today, entrance to the school grounds is via the city of Holon.
- Mikve Israel Encyclopedia of Zionism and Israel, edited by Raphael Patai, New York, 1971
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- An Agricultural School and Pioneer Settlement: Mikve-Yisrael in 19th Century Palestine, Ran Aaronsohn