He was born in the town of Tomaszów Lubelski in the southeastern border region of the Kingdom of Poland, and educated in Odessa, where he studied law but was unable to practice because of restrictions on occupations available to Jews.

In his early years, Pinsker favored the assimilation path and was one of the founders of a Russian language Jewish weekly (see also: Haskala).

Pinsker knew that a combination of mutually exclusive assertions is a characteristic of a psychological disorder and was convinced that pathological, irrational phobia may explain this millennia-old hatred, wherein: ... to the living, the Jew is a corpse, to the native a foreigner, to the homesteader a vagrant, to the proprietary a beggar, to the poor an exploiter and a millionaire, to the patriot a man without a country, for all a hated rival.His visit to Western Europe led to his famous pamphlet Auto-Emancipation, subtitled Mahnruf a seine Stammgenossen, von einem russischen Juden (Warning to His Fellow People, from a Russian Jew), which he published anonymously in German on 1 January 1882, and in which he urged the Jewish people to strive for independence and national consciousness.

In his 1882 pamphlet Auto-Emancipation, Pinsker argued against Palestine as the destination for a Jewish commonwealth:We must not attach ourselves to the place where our political life was once violently interrupted and destroyed.

If so, all the better, but first of all, we must determine—and this is the crucial point—what country is accessible to us, and at the same time adapted to offer the Jews of all lands who must leave their homes a secure and unquestioned refuge, capable of being made productive.

[4]Despite being urged several times to amend his essay to say that Palestine was the only acceptable Jewish refuge, Pinkser refused, even writing in his will that he had not retracted his opinion.

Moshav Nahalat Yehuda, now a neighborhood in Rishon LeZion, is named after him, as well as a street in Tel Aviv and several other locales in Israel.