In 1536 A.D., the Mughal Emperor Humayun, after his conquest of Gujarat, had visited Burhanpur & Asirgarh via Baroda, Broach (Bharuch) & Surat.
Raja Ali Khan (1576-1596 A.D.), also known as Adil Shah, was asked to submit to Akbar, when the latter had sent an expedition to Khandesh, in the summer of 1577 A.D. To avoid an unequal contest with the mighty Akbar, Adil Shah dropped his royal title and accepted the Suzerainty of Akbar. This marked an important event in the Deccan policy of the Mughals. Khandesh was used as a base for the future Conquest of Deccan.
Raja Ali Khan constructed many buildings like Jama Masjid at Asir fort in 1588 A.D., Jama Masjid at Burhanpur in 1590 A.D., Idgah at Asir, mausoleums & Serai at Burhanpur & Serai & Mosque at Zainabad.
Prince Khurram was nominated as the Governor of the Deccan in 1617 AD, by Jahangir to succeed Prince Parviz, and was bestowed the title of Shah by Jahangir.
Khurram led the Mughal army to a peaceful victory. Jahangir was pleased with his success & conferred him the title of Shah Jahan on 12th October, 1617 AD.
After the death of Jahangir in 1627, Shah Jahan ascended the throne of Mughal empire. Due to troubled conditions in the Deccan, he reached Burhanpur (Deccan) on the 1st March 1630, where he stayed for the two years, conducting operations against Bijapur, Ahmadnagar, and Golkunda.
On 7th June 1631, Shah Jahan lost his beloved & wife Mumtaz Mahal at Burhanpur, and her body was buried in the Garden of Zainabad, at the bank of river Tapti. Early in December of the same year (1631 AD), the remains of her body were sent to Agra.
Later on 6th March 1632, Shah Jahan left Burhanpur for the north, after appointing Mahabat Khan as the viceroy of the Deccan.
From the mid 16th Century to the early 18th century, the Nimar region (including Burhanpur, East Nimar,West Nimar Barwani District), was under the control of Aurangzeb, Bahadur Shah (Mughals), Peshwas, Sindhia, Holkar & Pawar (Marathas ), Pindaris etc. Later from early part of the mid 18th century, the management of the Nimar region came under Britishers.
Burhanpur district did not remain unaffected by the Great Uprising of First War of Independence in year 1857, which swept the country, against the British rule. In connection with the so called Riots of 1857, Tatya Tope had gone through the region of Nimar & before marching out of the region, burnt the police stations and Govt. buildings at Khandwa, Piplod and a number of other places and escaped again to central India by way of Khargone.
Burhanpur district was greatly affected during all freedom movements like Non-Co-operation movement, Civil Disobedience movement, Quit India Movement etc. During these movements, a near by District Khandwa was visited by Swami Dayanad Saraswati founder of Arya Samaj, Swami Vivekanand the great monk & founder of Ramkrishna Mission, Mahatma Gandhiji in 1921, Lokmanya Tilak etc.
Young Nationalists of the Nimar Region, like Haridas Chatterjee, Makhanlal Chaturvedi, Thakur Laxman Singh, Abdul Quadir Siddique has attended the Calcutta Session of Congress in 1917. Tilak has visited Khandwa during his whirl-wind tour to central province in 1918. The district did not fail to make its contribution in Non Cooperation Movement. Civil Disobedience Movement of 1930 has also been participated by many people of the district. Editor of swarajya, S.M.Agarkar was also arrested and imprisoned. Nav Jawan Sabha was established at Khandwa in 1931. Many students had also participated in this movement.
The District was created from East Nimar District and declared as separate district on 15th August 2003. Burhanpur town became the District HQ.