The history of Sheikhupura goes back to 100 BC. Historical research has established the fact that Sangla or Sakala was the capital of Punjab once, and it was here that Alexander the Great of Macedonia (known locally as Sikandar e Azam) fought one of his most serious battles of his career. Its name is spoken of, firstly in the pages of Tuzk-e-Jahangiri as Jahangirpura, after the name of Prince Salim Nur u Din Muhammad Jahangir. The fourth Mughal emperor of India named Jahangir changed the name of the city from Virkgarh to Sheikhupura after converting the majority of the population to Islam. This area belongs to the virk Jats. Virk jats created a fort in the vicinity of current day Sheikhupura and called it VirkGarh., i.e. "citadel of the Virks"

Mughal Emperor Nor-u-Din Muhammad Jahangir renamed the Virkgarh to his nickname of Sheikhu. In 1607, Sheikhupura was constructed following an order of Jahangir. The father of Jahangir, Emperor Jalal-uddin Mohammad Akbar use to call him Sheikhu (a nickname). During Sikh rule the new city was named Singhpuria, previously was known as Jahangirabad. The Sikh Misl named "Singhpuria" under the leadership of Nawab Kapur Singh Virk occupied the city and started calling it singhpuria instead of Virkgarh.

During the reign of Emperor Jahangir (1605 to 1627), Sheikhupura had the status of royal hunting ground. In Tuzk-e-Jahangiri, Jahangir wrote during the events in 1607:

“On the day of Tuesday, I reside in Jahangirpura, my hunting ground. According to my order, a Minar and a grave for my deer, Mansraj, were constructed here.”

Mughal Emperor Jahangir granted the estate of Sheikhupura to Syed Usman, the father of Shah Bilal, a religious preceptor of the line of Qadiriyyah.

Over the whole district, the period between the decline of the Mughal Empire after the death of Mughal Emperor Aurangzeb and the rise of Sikh confederacies was one of utter confusion and anarchy. The successive shocks of invasion from the northwest, and the devastation caused again and again by the invading armies of Nadir Shah.

Nader Shah and Ahmad Shah Abdali (1724–1773) almost completely ruined the prosperity of the tract. After the death of Aurangazeb, Muslim power declined and the Sikhs who occupied the region and ruled through various misls or small to medium sized groups. Nadir Shah and Ahmad Shah Abdali led raids that further weakened local Muslim rule. Several raids were made by the Bhangi Sardars, a Sikh community. Finally around 1780, Ranjit Singh, a Sikh ruler defeated the grandson of Ahmad Shah Abdali and later occupied this district. The Sikhs were defeated by the British around 1850 and it stayed under British rule until 1947.

In 1851, Sheikhupura Tehsil became part of Gujranwala District. The Artimapal Secretary Chief Commissioner Lahore wrote a letter to the Department of Wealth in 1855 to combine the Sheikhupura Tehsil with the Lahore District but it was never done. As soon as it became a District Zillah, a lot of lawyers came to practice. Under Sir Ganga Ram, district courts and hospitals were constructed in the city.

Shaihupura in pre-partition era (before 1947) was a prosperous land of traders and had a healthy mix of Hindus, Sikhs and Muslims. However, the partition saw bloody conflicts leading to mass migration of Hindus and Sikhs from Pakistan to India. The major Indian newspapers in that time quoted in the month of August 1947 - "Shaikhupura no more..." to express the extent of killings that Shaikhupura witnessed.

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