MS St. Louis was a diesel-powered passenger ship properly referred to with the prefix MS or MV, built by the Bremer Vulkan shipyards in Bremen for HAPAG, better known in English as the Hamburg America Line. The ship was named after the city of St. Louis, Missouri. Her sister ship, MS Milwaukee, was also a diesel powered motor vessel owned by the Hamburg America Line. St. Louis regularly sailed the trans-Atlantic route from Hamburg to Halifax, Nova Scotia, and New York City, and made cruises to the Canary Islands, Madeira, Spain; and Morocco. St. Louis was built for both transatlantic liner service and for leisure cruises.

The Holocaust, also known as the Shoah, was the genocide of European Jews during World War II. Between 1941 and 1945, Nazi Germany and its collaborators systematically murdered some six million Jews across German-occupied Europe, around two-thirds of Europe's Jewish population. The murders were carried out in pogroms and mass shootings; by a policy of extermination through labor in concentration camps; and in gas chambers and gas vans in German extermination camps, chiefly Auschwitz-Birkenau, Bełżec, Chełmno, Majdanek, Sobibór, and Treblinka in occupied Poland.Germany implemented the persecution in stages. Following Adolf Hitler's appointment as chancellor on 30 January 1933, the regime built a network of concentration camps in Germany for political opponents and those deemed "undesirable", starting with Dachau on 22 March 1933. After the passing of the Enabling Act on 24 March, which gave Hitler dictatorial plenary powers, the government began isolating Jews from civil society; this included boycotting Jewish businesses in April 1933 and enacting the Nuremberg Laws in September 1935. On 9–10 November 1938, eight months after Germany annexed Austria, Jewish businesses and other buildings were ransacked or set on fire throughout Germany and Austria on what became known as Kristallnacht (the "Night of Broken Glass"). After Germany invaded Poland in September 1939, triggering World War II, the regime set up ghettos to segregate Jews. Eventually, thousands of camps and other detention sites were established across German-occupied Europe.

The segregation of Jews in ghettos culminated in the policy of extermination the Nazis called the Final Solution to the Jewish Question, discussed by senior government officials at the Wannsee Conference in Berlin in January 1942. As German forces captured territories in the East, all anti-Jewish measures were radicalized. Under the coordination of the SS, with directions from the highest leadership of the Nazi Party, killings were committed within Germany itself, throughout occupied Europe, and within territories controlled by Germany's allies. Paramilitary death squads called Einsatzgruppen, in cooperation with the German Army and local collaborators, murdered around 1.3 million Jews in mass shootings and pogroms from the summer of 1941. By mid-1942, victims were being deported from ghettos across Europe in sealed freight trains to extermination camps where, if they survived the journey, they were gassed, worked or beaten to death, or killed by disease, starvation, cold, medical experiments, or during death marches. The killing continued until the end of World War II in Europe in May 1945.

The European Jews were targeted for extermination as part of a larger event during the Holocaust era (1933–1945), in which Germany and its collaborators persecuted and murdered millions of others, including ethnic Poles, Soviet civilians and prisoners of war, the Roma, the disabled, political and religious dissidents, and gay men.