About the early life and career of Reza Khan little is recorded. We know that he was born in a Shia family of Shiraz in Iran (or Persia), probably in 1717, the third of the four sons of Saiyid Hadi Ali Khan, the physician. Muhammad Husain Khan, the eldest son, was his full brother; Muhammad Ali Khan, the second, and Muhammad Ismail Khan, the youngest son, were his half brothers, born of a different mother.

When the Khan was about ten years old his father migrated with his four sons to India. India under the Timurids had always attracted men of talent and fortune seekers from Iran (which also included the Persianised and Shia dominated Iraq) and from Turan or Central Asia. The break-up of the Shia empire of the Safavids begun by the revolt of the Sunni or orthodox Ghilzai Afghans in 1709, and accelerated by ten years of full scale war thereafter, made the Mughal courts even more attractive to the fugitive noblemen from Iran. The Saiyid first took his family to Delhi, where his brother Naqi Ali Khan was a court physician and favourite of the Emperor Muhammad Shah (1717–48). Then, much later, they moved to Bengal where the Saiyid secured the post of Hakim or physician at Murshidabad, the capital of the province, thanks to the good offices of another Delhi court physician, ‘the complement of doctors, the reservoir of the physical and philosophical learning, the Galen of his time’, Alavi Khan. The move was made during the nizamat or governorship of Alivardi Khan (1740–56), probably not long after the invasion of Nadir Shah (1739) had destroyed and impoverished the city of Delhi.