In 1540 a deadly mutiny by Sher Shah Suri forced the Mughal Emperor Humayun to withdraw to Sindh, where he joined the Sindhi Emir Hussein Umrani. In 1541 Humayun married Hamida Banu Begum. She gave birth to the infant Akbar at Umarkot in the year 1542.
In 1556 the Ottoman Admiral Seydi Ali Reis visited Humayun; various regions of the South Asia including Sindh (Makran coast and the Mehran delta) are mentioned in his book Mirat ul Memalik. The Portuguese navigator Fernão Mendes Pinto claims that Sindhi sailors joined the Ottoman Admiral Kurtoğlu Hızır Reis on his expedetion to Aceh in 1565.
During the reign of Akbar, Sindh produced various scholars such as and others such as Mir Ahmed Nasrallah Thattvi, Tahir Muhammad Thattvi and Mir Ali Sir Thattvi and the Mughal chronicler Abu'l-Fazl ibn Mubarak and his brother the poet Faizi was a descendant of a Sindhi Shaikh family from Rel, Siwistan in Sindh. Abu'l-Fazl ibn Mubarak was the author of Akbarnama (an official biographical account of Akbar) and the Ain-i-Akbari (a detailed document recording the administration of the Mughal Empire). It was also during the Mughal period when Sindhi literature began to flourish and historical figures such as Shah Abdul Latif Bhittai and Sachal Sarmast became prominent throughout the land.