Mirkhvand was one of the most prominent historians during the reign of Sultan Husayn Bayqara (r. 1469–1506), well-known for his universal history, the Rawzat as-safa' (The garden of purity), which he wrote under the patronage of the high-ranking functionary Ali-Shir Nava'i (died 1501).

[2][3] Khvandamir likewise wrote under the patronage of Nava'i, dedicating his first works to him, the first one being the Ma'athir al-muluk (Memorials of the kings), a compilation of sayings ascribed to pre-Islamic and Islamic sages and rulers; and the second being the Khulasat al-akhbar fi bayan ahval al-akhyar (Summary reports on the affairs of those gone by), a concise version of the Rawzat as-safa'.

Following the co-succession of Badi al-Zaman and his brother Muzaffar Husayn to the throne in 1506, Khvandamir was installed as one of the two sadrs (head of religious fundings) of the entire kingdom.

[2][5] Khvandamir soon left for the neighbouring region of Gharjistan, where he briefly served Badi al-Zaman's son Muhammad Zaman Mirza (died 1540), who unsuccessfully attempted to establish his rule in the area.

Durmish Khan Shamlu (died 1526) was soon made the new governor of Herat, whose vizier Karim al-Din Khvaja Habiballah Savaji became the new patron of Khvandamir.

He accepted the invitation of the Timurid prince and Mughal emperor Babur (r. 1526–1530), who had in the same year established his authority over North India, including the cities of Delhi and Agra.