Yar Muhammad returned to Sindh in 1701 after Hifzullah's death and, along with his subordinate Shahdad Khan Talpur, retook his land making Khudabad his capital.

On the orders of Emperor Farrukhsiyar, Yar Muhammad and Mir Lutf Ali Khan, the new Subahdar of Thatta, laid siege to the town of Jhok which served as the base for Shah Inayat, a revolutionary and an agriculturalal reformist who led a peasants rebellion against the feudal landlords and estate holders of Sindh.

In 1725, Noor Mohammad Kalhoro, the son of Yar Muhammad and also the de facto ruler of Sind (who now had gained the administration of Bhakkar along with Sehwan), forged an alliance with the Emir of Afghanistan Hussain Hotak during his war with the Khanate of Kalat.

Sind officially broke away from the Mughal Empire in 1737 and asserted autonomy under Noor Mohammad and his Kalhora clansmen as the Thatta Sarkar too was alotted to him by Emperor Muhammad Shah.

Sind, along with Hyderabad and Awadh, supported the Mughal Empire during Nader Shah's invasion but was subdued by him in his Sindh expedition with Sibi given to Kalat and Shikarpur granted to Bahawalpur.

He also defended his territories during the Shikarpur campaign in which the Talpurs had to face the allied armies of the Afghans, Khan of Kalat and remnants of the Kalhora dynasty.