Jews began to settle in Annopol in the early 18th century. In 1765, the village was home to 395 Jews. In the second half of the 18th century, Hasidic Judaism was very popular among the local Jewish community. The successor of the Baal Shem Tov, Dov Ber (the Maggid of Mezritch; 1704-1772), lived in the village for a time, and was buried there. His disciple and successor, Meshulam Zusha, lived and taught in Annopol, and was buried there, as well. By 1784, after the massacre of local Jews during the Haidamak uprising, the Jewish population of Annopol had shrunk to 215. Annopol's Jewish community grew in the 19th century. In 1897, the town had 1,812 Jewish residents, who made up eighty-two percent of the total population.
On November 30, 1917, during the annual local fair, a pogrom was perpetrated by peasants from the area, and Jewish property was looted. In 1919, as part of the pogroms of the Russian Civil War, the Ukrainian army of Symon Petliura killed twelve Jews, including the head of Annopol's Jewish community, and looted Jewish property.
During the 1920s, under Soviet rule, a Yiddish school was opened in Annopol. A boarding school for Jewish children from the Slavuta region operated nearby. Some local Jews worked in large cooperatives. In 1926, Annopol was home to 1,278 Jews, out of a total population of 1,897. During the 1930s, many local Jews worked at a nearby kolkhoz, and in 1931 a Jewish rural council was established in Annopol. On the eve of World War II, there were some 300 Jewish families living in the village.
Annopol was occupied by German troops in July 1941. Shortly afterward, the Germans appointed a village elder. The Jews were ordered to wear yellow Stars of David on their chests and backs, and surrender all their valuables to the Germans. They suffered from frequent abuse. In July 1941, a group of about twenty-five Jews were taken out of the village, and some of them were shot by Ukrainian policemen. On July 28, 1941, some 200 Jewish men were shot outside the village by the 10th Infantry Regiment of the SS and Ukrainian policemen. In November 1941, the surviving Jews of Annopol – along with those from the nearby villages of Velikyi Sknit, Dolzhky, and Klepachi, who had previously been brought to Annopol – were moved into a ghetto that was set up in one of the village streets. On March 2, 1942, most of the surviving Jews were taken from Annopol to the Slavuta Ghetto. They were shot on June 26, 1942, during the liquidation of that ghetto, along with Jews from Slavuta, Berezdov, and Kilikiyev. Several artisans, craftsmen, and able-bodied men were left to work in Annopol and the surrounding area. According to a testimony, some of these Jews were later moved to the ghettos of Slavuta and Shepetovka, while the rest were shot dead near the local clinic. On August 10, 1942, following the successful escape of two women and men from the village, the Gendarmerie shot ten men and four women in retaliation.
Annopol was liberated by the Red Army in January 1944.