Around 1933, Jewish tradesmen were still active in all branches of the economy. Larger businesses were the Badische Möbelwerke, numerous wholesalers, and several cigar factories, one of which employed about 230 people.
In 1933, Heidelberg's Jewish population numbered about 1,100. There was apparently no organized anti-Semitism in Heidelberg before 1933, as no concrete anti-Semitic actions were known before the Nazi takeover, although Heidelberg had become a stronghold of the NSDAP in 1930. On the eve of April 1, 1933, Nazi members paraded through Heidelberg with banners calling on citizens to boycott Jewish businesses.
Under pressure from the Heidelberg NSDAP, the city no longer awarded public contracts; civil servants, employees, and workers were instructed to avoid Jewish businesses. The pressure on Jewish businesses was intensified by a campaign in the local newspaper "Volksgemeinschaft." As a result of the economic pressure, two-thirds of Heidelberg's Jewish businesses went bankrupt, and the rest were sold by their owners far below value.
By the end of 1938, the "Aryanization" of Jewish shops/businesses in Heidelberg had also been largely completed; of the approximately 100 businesses that existed in 1933, only two small businesses still existed at that time.
In 1933, the University of Heidelberg alone removed 55 professors and lecturers from their posts for "racial" reasons, among them the lawyers Ernst Levy and Walter Jellinek, the Romance scholar Helmut Hatzfeld, the dermatologist Siegfried Bettmann and the physiologist and Nobel Prize winner Otto Meyerhof.
On May 17, 1933, the student body of Heidelberg University also participated in the Nazi book burning. In 2013, a memorial plaque was dedicated to University Square.
By 1939, more than 800 Heidelberg Jews had left their hometown. From 1939 onwards, Heidelberg's Jews were increasingly segregated from the "Aryan" population; the mostly elderly Jews who remained in Heidelberg were forced to move into so-called "Jewish houses".
On October 22, 1940, the Jews of Heidelberg were also deported to the Gurs camp as part of the so-called "Bürckel Action". Of the approximately 300 Jews deported from Heidelberg, more than 80 died in Gurs and other internment camps in southern France; about 100 people were shipped from Gurs to the concentration camps of Eastern Europe between 1942 and 1944, where the vast majority also perished; only 70 people survived Gurs and other camps (through emigration). After the deportation, only just under 100 Jews lived in the city and district of Heidelberg; most of them were those who were married "in mixed marriages". Still, in February 1945, some of them were deported to Theresienstadt.
A memorial stone commemorates the victims of the deportation to Gurs.
Only 15 of the deportees returned to Heidelberg after the end of the war.
Immediately after the end of the war, a small Israelite community was able to re-establish itself in Heidelberg. It had prayer houses at various locations in the city.