Mandhana was born on 18 July 1996 in Mumbai to Smita and Shrinivas Mandhana.When she was aged two, the family shifted to Sangli in Maharashtra, where she completed her schooling. Both her father, and brother, Shravan, played cricket at the district-level, for Sangli. She was inspired to take up cricket after watching her brother play at the Maharashtra state Under-16s tournaments. At the age of nine, she was selected in the Maharashtra's Under-15 team. At eleven, she was picked for the Maharashtra Under-19s team.