The Delhi Sultanate and later Mughal Empire ruled the region. The Multan region became predominantly Muslim due to missionary Sufi saints whose dargahs dot the landscape of Punjab region. The city was founded in 1476 on the western bank of the Indus River and named after Nawab Ghazi Khan Mirani, son of Nawab Haji Khan Mirani, a Balochi chieftain, who had declared independence from the Langah Dynasty's Sultans of Multan. Together with two other Deras, Dera Ismail Khan and Dera Fateh Khan, it gave it's name to Derajat. After the decline of the Mughal Empire, the Sikh included Derajat. During the period of British rule, Dera Ghazi Khan district increased in population and importance.
The city was founded at the close of the 15th century and named after Nawab Ghazi Khan Mirani, son of Nawab Haji Khan Mirani, a Balochi chieftain, who had declared independence from the Langah Dynasty's Sultans of Multan. Together with two other Deras i.e. settlements, Dera Ismail Khan and Dera Fateh Khan, it gave its name to Derajat. Derajat eventually came into the possession of the British after the Sikh War in 1849 and was divided into two districts: Dera Ghazi Khan and Dera Ismail Khan. After the independence, many of the city's Hindu residents settled in Derawal Nagar colony of Delhi, India. The district of Rajanpur was later carved out of the Dera Ghazi Khan district. Some of them also settled in various part of India, including Bhiwani, Delhi, Jhansi, Ranchi, Ambala and Haridwar.