He faced minor rebellions on the eastern and western fronts of the sultanate during the initial years of his rule.

Amidst the chaos Muhammad Quli was still able to patronage art and establish the city of Hyderabad.

[3] From the time of his father Ibrahim Quli Qutb Shah, there was a high influx of populace into the city of Golconda, which led to over-crowding and unhygienic conditions.

It is said that once the sultan was coming back from a hunt and he crossed the bridge across River Musi and arrived at the flat land which pleased him.

[3] The city was planned in a gridiron manner with the Charminar in the centre and other important palaces and administrative buildings along the surrounding axes.

Other important buildings which were constructed in the following years such as Dar-ul-Shifa, Mecca Masjid, Badshahi Ashurkhana and several palaces which have since been demolished.

[8] Physicians who wrote Persian language books on Unani medicine during his reign include Mir Momin (Ikhtiyarat-i Qutub Shahi), Shamsuddin Ali Husain al-Jurjani (Tazkirat-i Kahhalin), Hakim Shamsuddin bin Nuruddin (Zubdat-ul Hukama), Abdullah Tabib (Tibb-i Farid), Taqiuddin Muhammad bin Sadruddin Ali (Mizan-ul Tabai'), Nizamuddin Ahmad Gilani (Majmu'a-i Hakim-ul mulk), and Ismai'l bin Ibrahim Tabrezi (Tazkirat-ul Hukama).