Five Jewish families from Pfeddersheim near Worms settled in 1650 as the city recovered from the devastation of the Thirty Years War (1618-48). Under the letter of protection accorded them in 1660, they were allowed to practice all crafts. With the approach of the French in 1689 (in the Nine Years War), many Jews fled while others participated in the defense effort. Most returned in 1690. In 1771 the community numbered 247 households and with its growing strength a tendency to tolerate its presence was seen in the municipal council. In 1807, Jewish students were enrolled in the municipal high school and in 1812, 25 Jews, mostly wealthy merchants, were enjoying full civil rights in the city. In the struggle for emancipation, new anti-Semitic outbursts came from various sectors of the local population. Nonetheless a Jew was elected to the city council for the first time in 1848. In 1852 the Jewish population was 1,803 (total 24,316). To accommodate the growing population a new synagogue was completed in 1854, equipped with an organ and served by R. Dr. Moses Praeger, whose Reform prayerbook was highly controversial.
The community maintained a broad range of charitable institutions. The Jewish hospital founded in 1711 was one of the earliest in Germany. In the second half of the 19th century, Jewish capital played a leading role in the city's burgeoning industry. Jews controlled the tobacco trade based on village plantations and ran flour mills, distilleries, tanneries, and textile factories. In 1871, a Jew was chosen for the first time as president of the local chamber of commerce and in 1914 a Jew was named president of the Baden Supreme Court.
By 1875 the Jewish population had grown to 3,942 and by 1910 to 6,402 (total 193,902). Intermarriage and conversion grew from the late 19th century. Jewish students in the city's high schools comprised 20% of the student body when Jews were less than 5% of the population. While the economic crisis struck at Jewish capital after WWI, Jewish commercial life remained active, with Jewish wholesalers operating 40 of the city's 66 textile outlets in 1930. Zionist activity revived, attracting many of the young. In 1929 a beit midrash was opened where a wide range of courses in Jewish subjects was offered. In 1933 the Jewish population was 6,509. It was characterized by an exceptionally high proportion of unmarried men and women and a relatively late age of marriage. With the onset of Nazi rule, Jews were increasingly dismissed from their jobs and their businesses undermined. Socially as well the Jews were isolated. After being banned from public bathing facilities in 1933 they were attacked on a popular private beach in summer 1935 by the SA in a mass Aktion where Jewish men were beaten and stripped to ascertain their origin and women molested. Over 600 Jews were signed up at the beit midrash, which by 1936 included 17 Hebrew classes along with courses in Arabic, English, French, and Italian. The Jewish Cultural Association (Juedischer Kulturbund) also offered a wide range of activities and social welfare services expanded to support the community economically. Children were gradually transferred into a Jewish school system, which embraced 454 students in 1936, and vocational training was offered to graduates as well as to the newly unemployed. The Zionist youth movements remained active, with 300 members as late as 1938. On “Kristallnacht” (9-10 November 1938), the main synagogue was blown up, large Jewish business establishments were targeted for destruction, and men under the age of 60 were sent to the Dachau concentration camp, where a number died. Priceless art objects were also destroyed in Jewish homes. Following “Kristallnacht” the last Jewish businesses, still numbering well over 500, were liquidated and within half a year, 240 children in the Zionist youth movements were taken to Palestine. In the entire 1933-40 period, 3,927 Mannheim Jews emigrated from Germany (119 of them were subsequently trapped in the German occupation). Of these, 1,451 reached the U.S.; 551 Palestine; 462 Latin America; and 1,159 various European countries. Nearly 2,000 were deported to the Gurs concentration camp in October 1940 and hundreds more were deported through 1945. In all, 2,375 perished in the camps, 40 committed suicide, and 67 died or were executed in detention. Another 14 were sent to Gurs (with one surviving) from the attached community of Feudenheim, where 113 Jews had lived in the late 19th century. After the war a new community was formed by East European refugees. It numbered 338 in 1977.