The building bearing the name of Pope Leo XIII originally belonged to the Sisters of the Little Company of Mary, known as the Blue Sisters. The Sisters were invited in 1894 by Archbishop Pietro Pace to come to Malta to manage a home for the sick. On their arrival they began their service at the provisional premises in Cathedral Street in Sliema and visited the sick in their homes. Since their services were highly appreciated, the sisters were then given support to open a bigger house for their mission.

The convent was inaugurated by Governor Grenfell in October 1900 and was named after Pope Leo XIII, in honour of the same pope who had approved the Little Company of Mary in 1882. Throughout the years, the house was expanded and used as a hospital including a maternity division. When the Blue Sisters were expelled from Malta in December 1980 this house was closed until new arrangements were concluded between the Archdiocese of Malta and the Maltese Government.

Casa Leone eventually reopened on the 16^th of December 1985 as an elderly home run by the Sisters of Charity after a substantial amount of structural works were carried out. It continued to be run by the Sisters of Charity until 2004. Since 2005, Casa Leone XIII continues to operate in this role as one of the homes for the elderly under the Archdiocese of Malta and the staff is now made up of 67 employees.