Jewish families began to settle in the city as early as the 13th century.

The medieval residential area was concentrated on the "Judengasse" (renamed "Dreikönigstrasse" in the 19th century), at the end of which the "Judentor" was located. A sign at the end of Dreikönigstrasse keeps the memory of the Judentor alive, which was demolished in the 18th century and hasn’t been reconstructed to the present day.

The community was destroyed in the pogrom during the plague in 1349. The property of the slain was confiscated.

However, immediately afterward, in 1350, the ruling Count-Palatine Ruprecht I took in persecuted Jews from Rhineland towns in Heidelberg, presumably to improve his financial situation by paying protection money. Numerous Jews owned houses and were granted further rights by Ruprecht I.

As a result, the synagogue was founded. Subsequently, the synagogue of the medieval community was built at Dreikönigstraße 25/corner of Untere Straße (on the site of today's building at Untere Straße 24). It had an extension of 8.4 by 14 meters in its interior and was probably designed as a hall building. It included a walled forecourt, a garden, and another building.

This second medieval community existed until the expulsion of all Jews from the Electoral Palatinate in 1390. All the properties of the Heidelberg Jewish community became the property of the university.

Shortly after the expulsion of the Jews (in September/October 1390) under Ruprecht II, the synagogue was consecrated by the Bishop of Worms as a church to the glory of God, Mary, and St. Stephen in a solemn service on the 2nd day of Christmas (December 26, 1390). For a long time it was the university chapel and the auditorium of the Faculty of Theology and Law, later also of the Faculty of Medicine. In 1689 the chapel burned down during the destruction of Heidelberg in the Palatine War.

In the following centuries, only very few Jewish families lived in Heidelberg. The city council and the city's guilds repeatedly ensured that the ruling Elector limited the number of "his" Jews in Heidelberg so as not to allow Jewish competition to grow. An extremely high municipal taxation of the Jews temporarily residing here also served this purpose.      

Only after 1648 were some families able to settle in Heidelberg again.

At the beginning of the 18th century, there were eleven families, whose number increased to 18 to 20 families in the course of the following decades.

In 1701, another Jewish cemetery was opened in the city (there were two predecessor cemeteries) in Klingenteichstraße above the Klingentor. It served as a burial place not only for Jews from Heidelberg but also for those from the surrounding area.

This old cemetery was closed in 1876 and is therefore not freely accessible. There are 180 gravestones, the oldest dating back to 1784. The wrought-iron entrance gate is decorated with two round discs showing a dove with a palm branch in its beak as a sign of life and an arm with a sickle as a symbol of death.

Those buried here enjoy, according to their faith, the right of rest until the resurrection. Therefore, the graves must stay untouched.

In 1724, the first Jewish student was enrolled in Heidelberg: Seligmann Elkan Heymann Bacharach from Mannheim.

In 1728, a Jewish student received his doctorate at the university for the first time.

During the so-called "Hepp-Hepp" riots in 1819, there were terrible pogroms against Jewish families. Jewish houses and stores were demolished and looted with axes and crowbars. Neither the police nor the citizen's guard intervened. Only armed students of the university came to the aid of the attacked Jews.

In the late 18th century there was an increased influx of Jewish families - probably never more than 20, who could only secure a right to live in the city by paying regular protection money.

The new Jewish Cemetery was opened in 1876 and is located within the grounds of the Bergfriedhof. However, it is an independent cemetery and is owned by the Jewish Religious Community and is still available for burials today. In 1904, the cemetery was extended to the higher slopes. Finally, in 1907, the mortuary was built.

For the time being, however, the newly established congregation was not allowed to build a synagogue, so services were held in private houses.

April 12, 1878: Inauguration of the then new synagogue in Große Mantelgasse on today's Synagogue Square. The community centre was located right next to the synagogue.

Since the end of the 19th century, the liberal spirit of Heidelberg University attracted prominent Jewish professors and numerous students who helped the university flourish.

On Pogrom Night in November 1938, the synagogue was set on fire by SA people. The synagogue was completely destroyed. The Torah scrolls and ritual objects stolen from the synagogue were taken to the police station. National Socialist-minded Heidelberg citizens and especially students burned them on the University Square about a week after the destruction of the synagogue.

After World War I, an Orthodox community ("Verein gesetzestreuer Juden in Heidelberg") had also formed due to the influx of numerous Jews from Eastern Europe; it was officially constituted in 1921. Since 1932, it had a prayer room in a rear building on Plöck. This synagogue room, furnished with the help of donations, had room for about 50 men and 30 women; there was a ritual bath in the building.

The Orthodox synagogue was also vandalized on November 10, 1938, but was rebuilt. In February 1939, the synagogue was demolished at the expense of the Jewish community.

In 1925 the highest number of Jewish inhabitants was reached: 1,412 people. In the economic as well as the university life of the city, the Jewish minority played a significant role at the beginning of the 20th century.

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.

In 1978, the synagogue square, which had initially been used as a parking lot, was turned into a park; another complete redesign was undertaken in 2001. Since then, the layout and various details of the former synagogue have been highlighted in the paving. A memorial stone has also been placed in the area of the former Torah shrine. In 2004, plaques with the names of the 292 people deported from Heidelberg to Gurs in 1940 were placed on the north wall of the house at Große Mantelgasse 3 (former rabbi's house).