At the end of the 18th century, a vibrant Jewish community emerged in Winschoten, primarily composed of migrants from Germany and Eastern Europe. Before World War II, Jewish residents made up about ten percent of the population, earning Winschoten the nickname "Lutje Mokum." The synagogue on Bosstraat served an important regional function, attracting Jewish visitors from surrounding villages. There was a Jewish cemetery and an active community life.

From 1940, the situation for Jewish residents changed drastically. At first, the changes seemed minor, but systematic exclusion soon began. In July, registration became mandatory, and 422 Jewish residents were officially recorded. From that moment, the net slowly closed around them. In October, civil servants were required to sign an Aryan declaration, and Jews in government service lost their jobs. Jewish associations were banned, and children were no longer allowed to attend regular schools. Jewish entrepreneurs lost their businesses, and access to markets and events was denied. The mandatory Jewish star followed on May 2, 1942.

In June 1942, the deportations began. Prior to this, medical examinations of the unemployed were conducted, giving the false impression that they were being sent to labor camps. In reality, this marked the beginning of rapid deportation. In less than two months, most of the Jewish community was transported via Winschoten Station to Westerbork Camp. From there, they were sent to concentration or extermination camps in the East. Only a few returned.

A well-known former Jewish resident of Winschoten was Etty Hillesum. She lived there from the age of four to ten (1918–1924). Her father was the deputy headmaster of the local gymnasium, and the family lived on Oranjestraat. Today, a monument with a yellow rose bearing her name stands in the same street.

Author Jaap Meijer also lived in Winschoten. He was born there in 1912 and stayed until he was eleven, when his father died. Under the pseudonym Sal van Messel, he wrote a short poem describing his youth, his father, and the deportation train:

"Die leste traain dij mie bie winschoot langs naar schanze ridt lag onder dizze zulde locht mien jongenstied dag dode pabbe doe ligst hail dicht bie woarhèn goan wie."

Translation: "The last train that passes me by Winschoten on its way to Schanze lay under this sultry sky, my boyhood years. Farewell, dead father, you lie so close by. Where are we going?"