Sir Peregrine Simon went to Westminster School and studied law at Trinity Hall, Cambridge. He was called to the Bar by the Middle Temple in 1973, and joined Brick Court Chambers, where he practised commercial law. He was appointed Queen's Counsel in 1991, and became a Recorder in 1998 and a Deputy High Court Judge in 1999. He was made a Queen's Bench Judge, nominated to sit in the Commercial Court, in 2001. He also sat occasionally in the Chancery Division and in tax cases in the Upper Tribunal. In becoming a High Court Judge, he followed his father, Lord Simon of Glaisdale, who was President of the Probate, Divorce & Admiralty Division in the 1960's and a Lord of Appeal in Ordinary in the 1970's. Sir Peregrine was a Presiding Judge on the North Eastern Circuit from 2006 to 2008. He was a Lord Justice of the Court of Appeal from 2015 to 2020. On retirement, he returned to practice as an international arbitrator.

A keen naturalist, Sir Peregrine was Vice-President of the Council of the Zoological Society from 1995 to 1996.