In 1536 John, 8th Baron Scrope supported the Pilgrimage of Grace rebellion against the religious reforms of King Henry VIII and gave Adam Sedbar, Abbot of Jervaulx sanctuary in the castle.

In consequence John Scrope had to flee to Skipton pursued by the King's men but Abbot Sedbar was caught and executed.

After her defeat in Scotland at the Battle of Langside in 1568 she fled to England, posing a threat to the position of the Protestant Queen Elizabeth I. Mary was initially held at Carlisle Castle under the watch of Henry, 9th Baron Scrope, but Carlisle proved unsuitable and in July 1568 Mary was moved to Bolton.

Her primary keeper at this location was Sir Francis Knollys who described the castle, appraising its security;[6]This howse appeareth to be very strong, very fayre, and very stately after the olde manner of building, and is the highest walled house I have seen, and has but one entrance thereinto.

[10] Mary obtained an "old cloth of estate" from Scotland, which she placed above her chair in the castle's great chamber, making it like a throne room.

[10] In January 1569, Mary was removed from Bolton Castle for the last time, being taken to Tutbury in Staffordshire where she would spend much of the 18 years before her execution in 1587.

[13][14] After the death in 1630 of Emanuel Scrope, 1st Earl of Sunderland without any legitimate children, Bolton Castle was inherited by Mary, the eldest of his three illegitimate daughters.

The castle is currently owned by their descendant, Thomas Peter Algar Orde-Powlett, 9th Baron Bolton, who inherited on his father's death in June 2023.