Most of Cherkassy's Jews were merchants or artisans. In Cherkassy there was a sugar factory owned by the Jewish sugar magnate and philanthropist Israel Brodsky and a tobacco factory owned by Aharon Zaritsky. In the 19th and early 20th centuries Cherkassy had three private Jewish schools for boys and one for girls.
In late 19th century the town had a branch of the proto-Zionist Hovevei Zion movement, and in the early 20th century Zionist groups were active in the town. There was also a branch of the socialist, anti-Zionist Bund in Cherkassy. The prominent Yiddish writer Moshe Litvakov was born in Cherkassy in 1875.
Pogroms were carried out in Cherkassy in 1881 and 1905.
Jews suffered greatly from the violence accompanying the years of revolution and civil war in Russia. During the civil war the ruling power in Cherkassy changed as many as ten times and each change of rulers was accompanied by pogroms against the local Jews. Approximately 1,000 local Jews lost their lives in three pogroms in 1919 carried out by various warring parties and much Jewish property was looted or destroyed.
The ban imposed by Soviet authorities on private economic activity forced many of the Jews of Cherkassy to search for new occupations. Several hundred local Jews found employment at local factories. Others turned to agriculture and joined three collective farms established near the town. Tseirei Zion and Maccabi organizations existed in Cherkassy well into the 1920s. In the 1920s a court chamber with deliberations in Yiddish was established in Cherkassy and there was also a division of the local police where Yiddish was the working language. In the 1920s and until the late 1930s, there were two Yiddish secondary schools and a Jewish vocational school with Yiddish as a language of instruction. In the early 1920s the Yiddish cultural organization Kultur Lige maintained several Yiddish libraries in the city. In the late 1920s the Yiddish newspaper "Dos komunistishe Wort" (The Communist Word) was published in Cherkassy.
In 1939 the 7,637 Jews living in Cherkassy comprised 14.8 percent of the city's total population.
After the German invasion of Poland in September 1939, a number of Polish Jewish refugees fled to Cherkassy.
Apparently many Jews succeeded in leaving Cherkassy before the city was occupied by German troops on August 22, 1941. By October 2 those Jews who remained in the city were ordered to register and to wear armbands. A three-man Jewish council was established and made responsible by the occupation authorities for controlling the local Jews and supplying Jewish labor to meet the needs of the occupiers. In mid-October 1941, on orders of the Ukrainian administration and the Ukrainian county police, Cherkassy's Jews were confined to a ghetto consisting of three streets in the city's Mytnitsa neighborhood.
The ghetto of Cherkassy did not exist for long since most of its inmates were murdered in late 1941.
Several dozen Jewish children in an orphanage directed by the Ukrainian woman Aleksandra Shulezhko were saved by its director, who in 1996 was recognized by Yad Vashem as one of the Righteous among the Nations.
Cherkassy was liberated by the Red Army on December 14, 1943.