Rabbi Tzvi Hirsch Kalischer was born in 5555 (1795) in Lissa (today Leszno), in the Posen region then under Prussian rule, to Rabbi Shlomo Kalischer and Rachel. He studied under Rabbi Yaakov of Lissa, author of Chavot Daat, and then in Posen under Rabbi Akiva Eiger, of whom he became a leading disciple. He also acquired broad learning in Jewish philosophy and Kabbalah.

After his marriage he settled in Thorn (Toruń), where he spent the rest of his life. For some forty years he served there as rabbi and dayan without accepting any salary, while his family lived from a small shop run by his wife. Like his teacher, he fought the early Reformers.

He was one of the forerunners of Zionism. As early as 1836 he wrote to Amschel Rothschild, setting out the idea of a redemption of Israel through natural means rather than waiting for miraculous intervention. In 1860 he convened a conference in Thorn for the settlement of the Land of Israel, which led to the founding in Frankfurt of a society for settling the land. In his book Derishat Tzion (1862) he argued that Jewish settlement of the land and the fulfillment of the commandments tied to it would be the first stage of redemption. He encouraged the Alliance Israélite Universelle to support agriculture in the Land of Israel and to found the Mikveh Israel agricultural school.

A renowned Talmudist, he wrote Moznayim LaMishpat on Choshen Mishpat, Emunah Yesharah on faith and philosophy, the glosses Tzvi LaTzaddik on the Shulchan Aruch, a commentary on the Torah and a commentary on the Pesach Haggadah.

All his life he longed to settle in the Land of Israel himself, but never managed to do so. He passed away in Thorn on 5 Cheshvan 5635 (October 16, 1874) and was buried there with great honor; the town's Jewish cemetery was destroyed by the municipality in 1974. Kibbutz Tirat Tzvi is named after him.