Thornleigh College was founded in 1925 by the Salesian Society at the request of the Clergy of Bolton.
It became a Direct Grant Boys' Grammar school catering for a wide area in Lancashire. In 1979, following the reorganisation of Catholic schools in Bolton to a comprehensive system, Thornleigh joined with St Anne's High School, to form a six form entry Voluntary Aided Mixed Comprehensive School with a Sixth Form Centre to serve the needs of all Catholic Sixth Form pupils. Catholic Secondary Schools in Bolton reorganised again in 1986, and Thornleigh combined with St Cuthbert's school, which had been founded in 1963, to form a new seven form entry Voluntary Aided Mixed Comprehensive School with a Sixth Form centre which continues to serve the whole of the borough. The school is under the Trusteeship of the Salesians of Don Bosco.
For ten years from 1980 Thornleigh was a split site school. £4 million of investment in new buildings in the years 1986 to 1989 enabled the whole school to consolidate at Sharples Park from September 1990. A new building for the Sixth Form was opened in 1987 and an £800,000 extension was added to it in 1995. A five class room extension for 11-16 pupils plus a new two storey dining room, costing £1.1 million in total, were added during 2000. In 2004, Thornleigh received a Sports College and Investor in People status.
On the same site is the Thornleigh Sixth Form. The head of the Sixth Form is Fr. Andrew Waller SDB. In total (2002), there are currently 1624 students at Thornleigh, with 370 studying at the Sixth Form.
The school is currently managed by a group of governors and Mrs Burrows is the current headmistress.
Fr Martin Coyle, the previous headteacher, stepped down in July 2007 and Mr Almond was appointed temporary head teacher until January 2008. The new headteacher, Mrs Burrows has been in place since Mr Almond's departure. Assistant headteacher Mr Roach left at the same time as Mr Almond, moving to Mount Saint Joseph Secondary School as a headteacher.