According to the 1939 census, more than 37 thousand Jews lived in the city, who made up one fifth of the townspeople. According to rough estimates, more than 20 thousand Jews became victims of the Holocaust in Vitebsk during the three years of occupation. Already in 1959, the census showed that the Jewish population of the city decreased by one third to 10.3 thousand people.

An accurate calculation of the victims of the occupation is made difficult by the lack of information on the number of Jews drafted into the Red Army who managed to evacuate from the city and arrived in the city from other regions of Belarus and surrounding villages before the occupation. In addition, in September 1943, the Nazis destroyed the remains of victims in places of mass executions.

German troops occupied the city on July 11, 1941. In the early days, the invaders shot and hanged Jews in the Jewish Staro-Ulanovichskoe cemetery and in the city garden named after Lenin. From July 17, 1941, the compulsory registration of Jews began. The descendants from mixed marriages and those who had relatives of Jews in the third generation were also subject to accounting. Registration documents were not preserved, but according to historians, 16 thousand people were on the lists.

An order to create a ghetto on the right bank of the Dvina appeared on July 25, 1941. The occupiers forbade the Jews crossing from the left bank to use the pontoon bridge and ordered the use of improvised means.

The Nazis identified an area with non-residential premises for the ghetto, limited by the streets of Engels, Komsomolskaya, Ilyinsky, Kirova and Naberezhnaya. According to rough estimates, there were up to 13 thousand Jews. The ghetto was of a closed type, its inhabitants were not supplied with food, and in the first days, the prisoners had to use river water due to the lack of a water supply.

In the first months, Jews survived by exchanging things for food from the local population. In September, authorities issued a decree forbidding citizens to appear near the ghetto. According to the estimates of historians, from 30 to 70 prisoners died every day, and by October 1941, 5,000 people died.

In August, Einsatzgruppe 9 arrived in Vitebsk, who carried out raids in the surrounding villages, punitive actions in the city and began the mass extermination of Jews near the village of Sebyakhi.

The Nazis carried out the liquidation of the ghetto from the end of October to the beginning of November 1941. There were six places of mass executions in Vitebsk and its environs. In 1993, commemorative signs were erected in the area where the ghetto was located, and in 1995 and 2000 on the outskirts where the shootings took place.

There is an urban legend that prisoners of the ghetto found an underground passage that led to the right bank of the Dvina and further to Polotsk, and some of them managed to escape. The legend is not confirmed by facts, but there are known cases of rescuing Jews by underground and local residents, two of whom received the title “Righteous among the Nations of the World”.