Perrot was reputed to be the son of King Henry VIII of England and Mary Berkley, who later married Thomas Perrot of Pembrokeshire. Knighted in 1547, he was appointed president of Munster by Queen Elizabeth I in 1570. After suppressing the Munster rebellion of James (Fitzmaurice) Fitzgerald, he pardoned the rebels and returned to England (1573). In 1584 he was sent back to Ireland as lord deputy. He confiscated vast lands in Munster for plantation by English settlers, but the colonization was poorly organized and executed. He did succeed, however, in bringing the native landowners of Connaught under English law by having them pay the crown a fixed money rent. In return, they avoided losing lands to plantations.

Meanwhile, Perrot's tolerance toward Roman Catholics and his plan to convert St. Patrick's Cathedral in Dublin into a university had earned him the enmity of Adam Loftus, Anglican archbishop of Dublin. In 1588 Loftus had Perrot recalled to England on trumped-up charges of treasonable negotiations with Spain. Perrot was found guilty, but he died in prison before he could be executed.