Rabbi Yaakov Tzvi Mecklenburg was born around 1785 in Lissa, in the province of Posen, then a great centre of Torah study, the son of Rabbi Gamliel. There he studied under the town's rabbi, Rabbi Zechariah Mendel, son of Rabbi David Tevele and a friend and correspondent of Rabbi Akiva Eiger.

He first went into business. In 1831, at 46, after commercial difficulties, he gave up trade and accepted the rabbinate of Königsberg in East Prussia, which he held for more than thirty years. The city's Jews were increasingly influenced by the Haskalah and Reform, which he firmly opposed; together with the Malbim he publicly fought the Reform rabbinical assembly of Braunschweig in 1844, which proposed, among other things, abolishing Kol Nidrei and permitting intermarriage.

His major work, HaKtav VehaKabbalah, is a Torah commentary demonstrating, through precise analysis of the Hebrew language, that the Oral Torah ("the kabbalah") is embedded in the very text of the Written Torah ("the ktav"). It was the first of a series of works published by Orthodox rabbis of his time to stem the Reform movement. First printed in his lifetime in 1839, it was reissued in an expanded edition in 1880 and is still studied and cited.

He passed away on 10 Nisan 5625 (1865).