The plains of Panipat lead to Delhi. In 1526, the Central Asian invader, Babur, defeated the ruling Afghans of North India at Panipat to establish the Mughal dynasty. Thirty years later, his grandson would re-establish the Mughal domain after his Hindu foe was beheaded at this same battlefield. The ruins of the Kabuli Bagh Mosque built by Babur in 1527 to commemorate his victory overlook these plains.

North India in the sixteenth century witnessed a three-way tussle for power between a small number of foreign Muslim newcomers from Central Asia: the Mughals, the much larger population of the more established foreign Muslims; the Afghans; and the huge population of indigenous Hindus. From this cauldron emerged a Hindu general, Hemu, the last Maharajah of Delhi is killed by a stray arrow at the Second Battle of Panipat. We know of Hemu's exploits from the accounts of Akbar's reign recorded by the Mughal historians, Abul Fazl in Akbarnama and Al-Badaoni in Akbar Shahi. The Mughals, who because of their Mongolian origins had only a thin Islamic veneer, would emerge victorious in this tussle, by suppressing their religious zeal and incorporating the Hindus into their military machine.

Babur died in 1530. His eldest son, Humayan, gave his four brothers separate provinces to govern. Kamran, who was given Kabul and Kandahar to govern, seized Punjab and forced Humayan to cede control of this territory to him. This deprived Humayan of the resources of Afghanistan and Punjab and weakened his position as Emperor. In 1535, Humayan invaded Gujarat and secured a major victory against its Sultan. When he returned to Agra, his addiction to opium caused him to neglect dealing with Sher Khan, the leader of the Afghans, until it was too late. In 1540, Humayan was decisively defeated by Sher Khan. He escaped capture and wandered as a homeless exile in Sindh and Marwar. In 1544, taking care to avoid capture by Kamran, he made his way to Persia where he was given asylum when he agreed to convert to the Shia faith.

The Shah of Persia financed Humayan's expedition against Kamran, to capture Kabul and Kandahar, on condition that Humayan cede Kandahar to the Shah after its capture.