Henry the VIII became king in 1509 at the beginning of his reign he left Cardinal Wolsey in charge of the government whilst he pursued private pleasures. When the Chancellor failed to secure the king's divorce from Catherine of Aragon from the Pope he was charged with treason. In 1534 Henry broke off relations with Rome ,and declared himself supreme head of the English Church. Henry died age 55 on the 28th January 1547.
In 1521 another Humphrey Stafford regained the Manor. Humphrey's father was executed at Tyburn as a traitor after the Battle of Bosworth field. At this time, his lands were taken from him and granted to Sir Edward Poyning. Sir Humphrey gradually restored the family to royal favour. He received a pardon from Henry VIII ,and in 1515 was granted a partial restoration of his land. At the time of his fathers death , Sir Humphrey was only eight years old , but was betrothed to Margaret Fogge daughter of Sir John. In 1532 he made a settlement of the manor on his further marriage with Joan, widow of William Lane. On his death in 1545 another Humphrey inherited Milton Keynes.

This Stafford died three years later leaving the manor to another Humphrey.

In 1548 this Humphrey Stafford became Lord of the Manor.( Edward VI came to the throne in 1547 until 1553 . Mary I 1553 to 1558) In 1555 he and his wife Elizabeth leased the site of the manor for twenty-one years to Laurence Woodall and his son Richard. This arrangement ended in a quarrel , as Thomas Digby alleged that Richard Woodall had transferred his interests to him rather than his son Thomas. In 1563 the manor retuned to Sir Humphrey Stafford , who later died in 1574.
Elizabeth I was crowned in 1558 her long reign ending in 1603. Unfortunately , during her reign 17,000 people died of the plague in 1563-4.

Sir Humphrey's brother John inherited the manor in 1574 dying in 1595. John's sons Humphrey of Sudbury in Eaton Socon and William of Blatherwyck of Northamptonshire came to an arrangement whereby William took the manor. On his demise in 1606 his son William, then a minor held the manor. In 1637 William's first son Edward held the manor, dying the following year leaving the manor to his brother Charles; who was succeeded by his younger brother William Stafford in 1643. He did not enjoy the profits of the estate. It was mortgaged for £6000 in 1634 to Sir Lewis Watson (who became Lord Rockingham) and John Loddington. Parliament were ignorant of this fact and granted Sir John Corbett the estate in recompense for losses caused by the kings troops. Corbett and Rockingham fought out their case in the Chancery and in 1652 it was referred to Parliament . Corbett pleading the Act of Oblivion. Rockingham died in1653 and his son Edward Watson and John Loddington joined William Stafford in levying for Milton Manor. Henry Stafford ,son of William ,was sued whilst a minor in1669 by Dr. Lewis Atterbury with regard to the glebe lands. In 1667 Henry Stafford conveyed the manor to Heneage Finch and his son Daniel.