Starting in 16th century, Jews from the Polish Crown had been settling in what is today southern Ukraine, working as merchants, importers and translators among the Cossacks in the Zaporozhian Sich.

After the abolition of the Zaporozhian Sich in 1775, when Russians took control over the area, Jews moved to the newly established coastal towns, one of them being[4]: 34–35  Khazhibei, which was renamed Odesa in 1795.

[a] Around this period, there were multiple Jewish religious institutions, including a burial society, a synagogue, and a school for orphans named Talmud Torah.

[4]: 35 Immigration to the region happened in two distinct waves during the first two decades of 19th century, on which the remote and newly formed Jewish community relied heavily for its growth.

As Steven Zipperstein argues, Jewish immigrants "looked upon Odesa, with its wide streets and limestone buildings, as a world apart from the ancient settlements to which they were accustomed, and Odesa came to represent to Jews elsewhere […] the option of a fresh start, offering a change in climate, economic possibilities, and perimeters of acceptable religious behavior".

According to a report from the latter year, the Jews possessed most of the city's commercial capital and dominated commodity trade in items such as silk, cotton, wool, hardware, iron, and shoes and largely controlled the export of salt.

[8]: 197  These new settlers grew aware of the potential importance of the Russian Black Sea port and were trying to profit from fluctuations on the grain market.

For example, on one evening in 1817, the city's rabbi Berish Ben Yisrael was beaten to death in the streets by a group of Jews who were unhappy with stringent observation of ritual law.

[4]: 46 [11]: 23 In the 1840s, the Brody Jews leased their first synagogue,[10]: 100  at the corner of Pushkin and Postal (now Zhukovsky) streets in a relatively small house, from the wealthy Greek businessman Ksenysu.

The major provisions regarding Jews under his reign included: conscription of Jews, including their children, which was passed in 1827; provisions regarding travel and settlement restrictions, signed into law in 1835; abolition of Qahal system in 1844; expulsions of Jewish populations from Kyiv, Kherson, and Sevastopol; and bans regarding use of Hebrew and Yiddish in public.

[16] Due to the blockade of Odesa port during the Crimean War and subsequent disruption of trade, the city's exports rapidly dropped tenfold from 1853 to 1855.

However, unlike the Greeks, the Jews were able to withstand the recession due to their close contact with the producers, which greatly improved their ability to assess the market and allowed them to trade with a smaller profit margin.

The term became common after a wave of large-scale anti-Jewish violence swept the southern Russian Empire, including Ukraine, between 1881 and 1884, incited by rumours blaming Jews for the assassination of Alexander II.

More than two million Jews fled Russia between 1881 and 1920, the vast majority emigrating to the United States and the Ottoman region that became Palestine, and the city became an important base of support for Zionism.

After arduous negotiations, the Russian government approved the establishment of the Society for the Support of Jewish Farmers and Artisans in Syria and Palestine, also known as the Odesa Committee, in early 1890.

[21]: 45  It was based in Odesa, headed by Leon Pinsker, and dedicated to practical aspects of establishing Jewish agricultural settlements in Palestine.

[23]: 915 Despite the efforts to promote Zionism and subsequent emigration, however, the share of Jews in the population of Odesa remained fairly constant, at about 35%.

[16] The SS Ruslan set sail from Odesa in 1919 carrying with it some of the future intellectual and cultural of Israel including the historian Joseph Klausner, the artist Yitzhak Frenkel Frenel, the architect Ze'ev Rechter.

On 23 October, with the arrival of Axis forces in the city, an order was issued directing all people of Jewish origin to report to the village of Dalnyk the following day; around 5,000 Jews obeyed.

After the war, Jews constituted more than ten percent of Odesa's population, and could be found in most occupational groups from port stevedores and unskilled workers to the intellectual elite.