The De La Salle School for Boys, established in the 1930s, was originally based at 9 Richmond Crescent, Cardiff at a site formerly occupied by St Peter's Catholic Young Men's Society.

In 1987, Dr David Neville became the founding headteacher of the new school, still located at Greenway Road, opening its doors to both boys and girls up to the age of 16; A Levels were introduced in 1996.

As the school roll grew, it became apparent that St John's had outgrown the site at Greenway Road.

In 1995 the college moved to its current site, Ty-to-maen, a mansion built in 1885–9 by the Cardiff architect E. Bruce Vaughan for Richard Allen of Spillers flour mills.

[4][5][failed verification] This led to St John's being named 'Welsh Independent Secondary School of the Year' in the Sunday Times 'Parent Power' annual supplement.

[10] They also managed to achieve the Fastest Car in UK History, recording 1.036 seconds at the 2021 Virtual National Finals.