Susan was born of Katherine, Duchess of Suffolk's second marriage to her Steward, Richard Bertie. The Duchess and Bertie were noted reformers, and when Susan was a baby the family left for exile in Geneva to escape the increasing persecution of Protestants. On their return to Grimshorpe, Lincolnshire, Susan was educated in a strongly Puritan atmosphere, under Miles Coverdale. During Susan's youth, her mother was custodian of Lady Mary Grey, following the latter's ill-advised marriage.
Susan married first in 1570, to Reynold Grey, whose claims to the Earldom of Kent were recognised in 1572. He died soon after, leaving Susan a childless widow at the age of 19. She married again, to Elizabeth I's displeasure, an army captain and moved to the Low Countries, where her son Peregrine was born. On being widowed a second time, she returned to England, where like her mother before her, she was a patron of education. In particular, the poet Emilia Bassano paid tribute to her as:
“The Mistress of my youth, the noble guide of my ungovern'd dayes"