In 1549, in the reign of the Protestant Edward VI, the college was dissolved, the priests turned out and all the rich trappings sold or destroyed. All Saints became a parish church.

In the reign of the Catholic Mary, it had its own Protestant martyr. Joan Waste was a poor blind woman living in the parish, who used to go daily to All Saints where the clerk would read the Bible to her. Joan could not accept the doctrines then being preached and was tried for heresy. She was burned as a heretic at the age of 22 at Windmill Pit.

At the beginning of the 17th century the connection between the Cavendish family and All Saints was strengthened in a grand manner by the building of an elaborate monument to Elizabeth, Countess of Shrewsbury, ‘Bess of Hardwick’, one of whose husbands was Sir William Cavendish. The association continued and for more than 200 years the Cavendishes – the family name of the Dukes of Devonshire – were buried here, including the equally famous Georgiana, Duchess of Devonshire, in 1806.

By the beginning of the 18th century, the Church was in a state of disrepair. In February 1723 the vicar, Michael Hutchinson, arbitrarily began its demolition (except the tower) overnight. For the new church he chose as architect James Gibbs, who had designed St Martin in the Fields in London. A local ironsmith, Robert Bakewell, was commissioned to make the now famous screen, which was put in place in 1730.

There were many changes of furnishings and the addition of galleries over the decades that followed, the acquiring of fine plate, notably that given by the Earl of Exeter, and a very large number of memorials to local worthies, but the buildings remained substantially unaltered until the second half of the 20th century.