Safed Sanjak (Ottoman Turkish: سنجق صفد; Turkish: Safed Sancağı) was a sanjak (district) of Damascus Eyalet (Ottoman province of Damascus) in 1517–1660, after which it became part of the Sidon Eyalet (Ottoman province of Sidon). The sanjak was centered in Safed and spanned the Galilee, Jabal Amil and the coastal cities of Acre and Tyre. The city of Safed was made up of Muslim and Jewish townspeople. At the same time the rest of the sanjak was populated by Sunni Muslims, Bedouins, Metouali Twelver Muslims, and Jewish and Druze peasants.

The territory of Safed Sanjak consisted of the area between the Zahrani River in the north to Mount Carmel (near Haifa) in the south, and the area between the Sea of Galilee in the east and the Mediterranean Sea in the west. Besides Safed, it included the port cities of Acre and Tyre and the entire Galilee and Jabal Amil area. The district had a mixed population of peasants and Bedouin. The inhabitants of the Jabal Amil region were predominantly Shia Muslim, specifically and historically called Mitwali, while the Galilee had a Sunni Muslim majority, including peasants and Bedouin, and a large Druze minority. The district also contained Jewish communities.

In the 16th century, the Safed Sanjak was divided into the following five nawahi (singular: nahiya; third-level administrative subdivisions) and a'mal (singular: amal; fourth-level administrative subdivisions):

There is no available information about the administrative divisions of Safed Sanjak during the 17th century. By the 18th century, Safed Sanjak was divided into ten nawahi.

Before Ottoman rule, Safed was the capital of its own mamlaka (province) of the Cairo-based Mamluk Sultanate. Administrative information about Mamlakat Safad derives mainly from two sources: the qadi (Islamic head judge) of Safed in the 1370s, Shams al-Din al-Uthmani, and the Mamluk historian al-Qalqashandi, who based much of his material about Mamlakat Safad on al-Uthmani's work. Most of the information about the mamlaka covers the period between 1260 and 1418, while little is known for the last century of Mamluk rule before the Ottoman conquest following the Battle of Marj Dabiq in 1516. Travelers' accounts from the 15th century describe a general decline of the region around Safed precipitated by famine, plagues, natural disasters and political chaos, and the flight of peasants from their villages to the main towns or their adoption of nomadism.

The Ottomans entered the territory of the mamlaka through the Daughters of Jacob Bridge and did not meet any resistance in or around Safed. They bypassed the city, setting up camps at the Daughters of Jacob's Bridge, Khan Jubb Yusuf, Khan al-Minya and Khan al-Tujjar, all located in the mamlaka, before proceeding to conquer Mamluk Egypt. While Selim I was in Egypt, rumors spread in Safed that he had been killed, spurring the townspeople to revolt against the Ottomans before being suppressed by the new authorities.

After its incorporation into the Ottoman Empire, Safed was reorganized into a sanjak administratively part of the Damascus Eyalet. Its jurisdiction roughly corresponded with the territory of Mamlakat Safad. Safed Sanjak prospered at least during the first sixty years of Ottoman rule, with displaced peasants returning to their villages and the town of Safed becoming a haven for Jews from Europe, who turned the town into a wool production center. The first known Ottoman land and tax survey in the sanjak was in 1525/26, followed by a second survey in 1538/39. The second survey shows substantial increases in the population and tax revenues, possibly a result of peasants returning to their villages and the stability brought by the early Ottoman rulers. In 1547–48, Safad Sanjak contained a total of 287 villages.

In the 16th century, the Sudun clan of Qana, who were Shia Muslims of purported Circassian origins, and the Al Shukr of Aynatha, a family of Shia seyyeds (religious leaders), dominated the Bilad Bishara nahiya of the sanjak.