Nicholas' elder brother Sir Adam Loftus was made Vice-Treasurer of Ireland during the administration of Thomas Wentworth while Nicholas was appointed as an Irish Treasury official, with the title Clerk of the Pells, under him.
He was elected as a member of the Parliament of Ireland in 1613 and 1634, representing the seat of Fethard in County Wexford.
[3] In 1623, he married Margaret Chetham, the daughter of Thomas Chetham, a prosperous landowner from Nuthurst (now New Moston), Lancashire, who later acquired an estate at Hacketstown, County Wicklow, and his first wife Mary Forster.
By his wife he had fourteen children, of whom six sons and five daughters reached adult life.
After his death in 1666, he was succeeded by his eldest son Sir Nicholas Loftus.