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John Luffe or Luff was born in 1647. His father of the same name had himself studied at Oxford: he became Vicar of Aylesbury, but was ejected for nonconformity, and remained in Aylesbury as a nonconformist minister.

Notwithstanding the fact that his father is described as a "minister" at the time of his matriculation, Luffe was admitted to the University of Oxford from Magdalen Hall on 4 December 1661 at the age of 14. He obtained his BA from Trinity College in 1665, his MA from St Mary Hall in 1668, and his B.Med. and D.Med. in 1673.

Luffe probably married his wife, Anne in the early 1670s. They appear to have lodged at first with Robert Wood (brother of the diarist Anthony Wood) at Postmaster's Hall in Merton Street, in the parish of St John the Baptist Church (Merton College Chapel). Robert is described as the uncle of their children, which implies that Anne may have been the sister of Robert's wife Mary Drope. Later they had a house immediately to the east of Logic Lane (then Horsmull Lane) in the same parish, but by 1680 they appear to be living in the parish of St Mary Magdalen.

John and Anne Luffe had the following ten children:

• Wilson was born on 1 September 1674 in the house of Robert Wood opposite Merton College and was baptised at St John the Baptist Church nine days later.
• Anne was born in the same house and baptised at St John the Baptist Church on 9 March 1675/6
• Mary I died 28 June 1678 in infancy, and was buried in the north part of the outer chapel of St John the Baptist Church, near the grave of Anne Wood, her cousin (daughter of Robert Wood)
• Mary II was born on 19 July 1679 baptised at St John the Baptist Church. She was buried on 31 January 1680/1 in the north part of the outer chapel, called the parish isle, of St John the Baptist Church
• John
• Hester (name recorded in register as "Easter") was baptised on 28 December 1680 at St Mary Magdalen Church
• Hannah was baptised on 9 January 1681/2 at St Mary Magdalen Church
• Elizabeth was baptised on 20 January 1682/3 at St Mary Magdalen Church. She died in St Mary Magdalen parish on 4 March 1682/3 and was buried inside St John the Baptist Church two days later.
• Mary III was baptised on 25 February 1685 at St Mary Magdalen Church.
• Katherine was baptised on 2 November 1685 at St Mary Magdalen Church.

There used to be a small square white gravestone to their first two daughters given the name Mary in St John the Baptist Church reading:

Here
lie the Bodyes
of MARY LUFFE the elder
who died ye 28 of June 1678
and MARY LUFFE the younger
who died June ye 30 1680
the Daughters of JOHN LUFFE
Dr. in Physick
and Anne his Wife.

Luffe was appointed Regius Professor of Medicine and admitted on Friday 1 July 1681, and remained in this post until his death "between 3 and 4 in ye morning" on 7 September 1698 at the age of 53. He was buried in St John the Baptist Church two days later, and there is a white marble slab, 16 inches square (set as a diamond) under the tower:

The "Will of John Luffe, Doctor of Physic of University of Oxford" was proved in the Chancellor's Court in Oxford on 14 December 1699 and at the Prerogative Court of Canterbury on 20 January 1699(ref PROB 11/449)

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Luffe's children

Wilson Luffe (b.1674) was buried in Merton College chapel on 9 December 1709.

Hester Luffe (b.1676) was buried in Merton College Chapel on 26 February 1709/10.

Anne Luffe (b.1676) married first Dr Henry Bull of Shapwick in Somerset, a Commoner of Magdalen College, at Magdalen College Chapel on 24 January 1692/3. She was described as being a native of the parish of St John the Baptist. Dr Bull died at Bath in August 1694, and on 15 June 1701 she became the second wife of the physician Sir Edward Hannes.

Mary Luffe III (b.1685) was buried on 30 September 1711 at St Mary Magdalen Church.

John Luffe was buried on 29 May 1714 in Merton College Chapel.

Hannah Luffe (b.1682) was buried on 12 February 1717/18 in Merton College Chapel. Her will was proved in the Chancellor's Court at Oxford on 20 February 1717/18.