St Cuthbert's was opened on All Saints' Day (1 November) 1893, to replace the independent 'Home for Friendless Girls' in Durham. The new establishment was situated in Pierremont Crescent. To mark the occasion, the Bishop of Durham came to Darlington and conducted a benediction ceremony (a type of blessing). This was held in the Home's schoolroom, which was crowded with interested local people.
St Cuthbert's could house up to 40 girls, who were aged 8-16. The younger children attended the local school, which was just a short walk from their home. The older girls were trained in housework, cooking and laundry-work by the four resident matrons. They even established a modest business, offering their laundry services to people living outside the Home. In 1903 they managed to raise over £200, which was around one-fifth of the Home's annual income. Such enterprise earned high praise for St Cuthbert's, and one of the Society's inspectors described it as 'one of the best homes he had visited.'
In 1909 the Executive Committee of St Cuthbert's established a building fund, with the intention of constructing a new house for the girls. At this time, it was the policy of the Society that half the funds of a new building should be raised at a local level. Once this had been achieved, the Society would meet the other half and construction would start. Various fundraising events were organised, as in 1914 when a 'Rainbow Bazaar' was held at the Temperance Hall, Darlington. Despite this success, building work was delayed throughout the First World War and it was only started in 1922. In 1923 St Cuthbert's Home for Girls moved to new premises in Cleveland Avenue, Darlington, and was officially opened on 11 December with a dedication ceremony conducted by the Lord Bishop of Durham.
St Cuthbert's closed in 1947, and re-opened as St Cuthbert's Nursery in 1949, continuing until 1978.