By the time the Ottoman Empire rose to power in the 14th and 15th centuries, there had been Jewish communities established throughout the region. The Ottoman Empire lasted from the early 12th century until the end of World War I and covered parts of Southeastern Europe, Anatolia, and much of the Middle East. The experience of Jews in the Ottoman Empire is particularly significant because the region "provided a principal place of refuge for Jews driven out of Western Europe by massacres and persecution."

At the time of the Ottoman conquests, Anatolia had already been home to communities of Byzantine Jews. The Ottoman Empire became a safe haven for Jews from the Iberian Peninsula fleeing persecution (see Alhambra Decree). By the end of the 16th century, the Ottoman Empire had the largest Jewish population in the world, with 150,000 compared to Poland's and non-Ottoman Ukraine's combined figure of 75,000.

The First and Second Aliyah brought an increased Jewish presence to Ottoman Palestine. The Ottoman successor state of modern Turkey continues to be home to a small Jewish population today.

At the time of the Battle of Yarmuk, on 15–20 August 636, when the Levant passed into Muslim rule, thirty Jewish communities existed in Haifa, Sh’chem, Hebron, Ramleh, Gaza, Jerusalem, as well as many other cities. Safed became a spiritual centre for the Jews and the Shulchan Aruch was compiled there as well as many Kabbalistic texts.

In addition to the already existent Jewish population in the lands the Ottomans conquered, many more Jews were given refuge after the expulsion of Jews from Spain under the reign of Beyezid II. Although the status of the Jews in the Ottoman Empire may have been exaggerated, it is undeniable that some tolerance was enjoyed. Under the millet system, non-Muslims were organized as autonomous communities on the basis of religion (viz. Orthodox millet, Armenian millet, etc.). In the framework of the millet, Jews had a considerable amount of administrative autonomy and were represented by the Hakham Bashi, the Turkish term for the Chief Rabbi. There were no restrictions in the professions Jews could practice, in contrast to the extensive restrictions common in Western Christian countries. There were restrictions, however, regarding the areas Jews could live in or work, which were similar to the restrictions placed on Ottoman subjects of other religions. Like all non-Muslims, Jews had to pay the haraç ("head tax") and faced other restrictions in clothing, horse riding, army service, slave ownership, etc. Although many of these restrictions were decreed, they were not always enforced. Jizya collected from Christian and Jewish communities was among the main sources of tax income of the Ottoman treasury.

Some Jews who reached high positions in the Ottoman court and administration include Mehmed II's minister of Finance ("Defterdar") Hekim Yakup Pasha, his Portuguese physician Moses Hamon, Murad II's physician Is'hak Pasha, and Abraham de Castro, who was the master of the mint in Egypt.^{[citation needed]}

The first Jewish synagogue linked to Ottoman rule is Etz ha-Hayyim (Hebrew: עץ החיים) in Bursa which passed to Ottoman authority in 1324. The synagogue is still in use, although the modern Jewish population of Bursa has shrunk to about 140 people.

During the Classical Ottoman period, the Jews, together with most other communities of the empire, enjoyed a certain level of prosperity. Compared with other Ottoman subjects, they were the predominant power in commerce and trade as well as diplomacy and other high offices. In the 16th century especially, the Jews rose to prominence under the millets, the apogee of Jewish influence could arguable be the appointment of Joseph Nasi to Sanjak-bey (governor, a rank usually only bestowed upon Muslims) of the island of Naxos. Also in the first half of the 17th century the Jews were distinct in winning tax farms, Haim Gerber describes it as: "My impression is that no pressure existed, that it was merely performance that counted."