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St. Francis Xavier's College was founded in 1842 by the Society of Jesus. It was opened by Fr. Francis Lythgoe and was to be conducted by masters from and in connection with the Jesuit College at Stonyhurst, near Blackburn.

The school at first occupied a house at 36, Soho Street, but in 1843 it moved to 43, St. Anne Street. Three years later it was established at Salisbury Street, where it was to remain until 1961. The imposing college building, which can still be seen on Salisbury Street, was erected in 1877.

In the years immediately before the second world war the decision was taken to move the college from the inner city to a site in the suburbs which could accommodate both the school and playing fields.  This led to the purchase of the High Lee estate at Woolton in 1941.

The playing fields at Woolton were brought into use in 1950 when those at Melwood, West Derby, which had been acquired in 1920, were sold to Liverpool Football Club. Eleven years later the College moved into its new accommodation at High Lee and the buildings at Salisbury Street were sold to Liverpool City Council.

In 1974 the trusteeship of the College was transferred from the Jesuits to the Brothers of Christian Instruction, who had come to Liverpool in 1961. They are the present trustees and continue to undertake the direction of the school.

In 1983 the College participated in the scheme of re-organisation of Catholic secondary schools in Liverpool. The buildings of the former Cardinal Newman Secondary Modern School on Queens Drive, Childwall, became the lower school of S.F.X, while the buildings at High Lee accommodated the upper school. Since 1983 the school has had a comprehensive intake of pupils from its neighbouring Catholic primary schools.

The opportunity for schools to opt out of local authority control was given by the Education Reform Act of 1988. In February 1989, the parents of boys at the school voted in favour of applying for grant-maintained status. The application was subsequently approved by the Secretary of State, and, in consequence, St. Francis Xavier's College opened a new chapter in its history in January 1990, when it assumed complete control of its own management with direct funding from the Department for Education.

The College celebrated its one hundred and fiftieth anniversary in 1992.

The College became coeducational in the sixth form in 1992

In 1996 St Francis Xavier's College was granted "Technology College" status for three years.

In 1999 the College retained control of its management when it assumed its new status as a ‘Foundation school.’

In 2002 the College achieved single-site status and ceased to occupy the Queens Drive Site.

In 2003 the College received ‘Healthy Schools Award’.

In 2005 the College was awarded ICT and Mathematics Specialist Status 

In 2012 the College became known as a Catholic Academy

St. Francis Xavier, the patron saint of the College, was born in 1506 in the castle of Xavier, a fortress in the Basque country of Navarre.

In 1525 he left Spain for the University of Paris, where he was to remain for eleven years. In Paris Francis Xavier made the acquaintance of Ignatius Loyola, who had plans for the formation of a body of men prepared to put their lives at the service of the Pope. These plans led to the foundation of the Society of Jesus - the Jesuit Order - which was given approval by the Pope in 1540. Francis Xavier, who had been received into the priesthood in 1537, was one of the original members of the new order.

In 1540 Francis was invited by the King of Portugal to lead a mission to the East Indies. In the following year he reached Goa, which he made the base for missionary work in India and Ceylon. Early in 1545 Francis left India for Malacca where he continued the work of conversion. It has been claimed that during this time he brought the Christian faith to the Philippines.

For many years Francis had the ambition of bringing Christianity to Japan. After much difficulty the mission set out in June 1549, and for the following two years he was engaged in preaching to the Japanese in their own language, which he had learned with some difficulty.

After returning to Goa in 1552, Francis set about organising a mission to China, which set out later in the same year. Francis and his companions reached the island of Sancian off the Chinese coast. However, although he was in sight of the mainland, he could continue no further having incurred an illness which proved fatal. He died in the early hours of Saturday, 3rd December 1552, at the age of 46.

A small church on Sancian marks the spot where Francis died, but his body was brought back to Goa where it remains to the present day.

When the Jesuits returned to Liverpool in 1842 to set up a school in association with Stonyhurst College, they dedicated it to St. Francis Xavier. His feast day is celebrated on December 3rd.

The Brothers of Christian Instruction were founded in 1817 by Jean Marie de la Mennais in order to teach the poor children of Brittany, whose religious and secular education had been sadly neglected in the wake of the Revolution and the Napoleonic regime. In 1819 another founder, Fr Deshayes, merged his own young congregation with that of Fr de la Mennais and it is at this date that the Society received its title and also its motto "God Alone".

Jean Marie Robert de la Mennais was born at St. Malo in Brittany on the feast of Our Lady's birth, September 8th, 1780. His father was a wealthy ship-owner who had rendered his province an eminent service by selling off his corn below cost price at a time of serious famine. Louis XVI honoured him by adding the title de la Mennais to the family name Robert.

John lost his mother when he was only seven but her deep piety and lively intelligence marked him for life.

He had early set his heart on being a priest and, despite the difficult times of the Revolution, he advanced rapidly in his studies and in spiritual growth under the tuition of Fr Vielle, a young priest in hiding, and Fr de Cloriere. The latter was a Jesuit priest and in 1790, during the Revolution, he founded the Daughters of the Heart of Mary, a Congregation which has today a house in Liverpool.

On February 25th, 1804, John was ordained a priest and in addition to his normal duties he immediately took up the work of education. This was to remain his overriding concern for the rest of his days and it was for its sake that he declined the bishopric on numerous occasions.

Like every servant of God, John de la Mennais was marked by the cross and he was the victim of the vilest accusations. But the hand of God was upon his work and such was the success of his Congregation of Brothers that they were soon in demand not only throughout France but also in its colonies and in England. The young men that Fr de la Mennais educated at Cardinal Wiseman's request were to form a separate congregation; and it is to this initiative that St. Mary's College of Education, Twickenham, owes its origins.

In 1903 the Congregation had a severe setback when by order of the Combes government all its schools in France and the colonies were closed. The French novitiate was immediately transferred to England. But in 1922 the Superiors of the Order found a more convenient house for it in Jersey and at the request of the Bishop of Portsmouth premises vacated at Southampton became a new school, St. Mary's College. It is now a primary and grammar school of some 800 pupils.

In 1961 the Brothers came to Liverpool and in September 1964 they began teaching at St. Francis Xavier's College. In 1974 they undertook the direction of the College.

The aim of the Brothers in Liverpool as elsewhere, whether in Tahiti, or Spain, or Canada, remains that of their Founder, "to make known Jesus Christ". It is only such an aim that could justify the sacrifices of so many parents and warrant the future of Catholic schools.