St. Luke's was the sixth Anglican church to be built in the City of Hamilton. It was originally created as a chapel of ease to meet the spiritual needs of the people in the neighbourhood known as the Lake District. The Lake District was included in the Christ's Church Cathedral parish boundaries, but the road to the Cathedral was very bumpy and bog-filled; St. Luke's provided an alternative place of worship. The original church was a wooden building once used by the Methodist Episcopal Church. It was purchased and moved from its location on Ferguson Avenue (north of Simcoe) to the current site at the corner of John and Macaulay.

The first service was held on July 9th, 1882. During the 1880's, the parish of St. Luke's strove to change its status from chapel of ease to that of an independent parish. That dream was achieved when Bishop Fuller appointed the Rev. William Massey in 1883 as Rector. The Parish boundaries are: Wentworth Street to the Bay, and from the Grand Trunk (CNR) tracks to the Bay.

The present church building, constructed in 1898, is a substantial brick building with a seating capacity for 300 worshippers. The old frame church was used as the Sunday School and meeting hall until 1920, when a new hall was built. The church has seen many changes and many rectors over the years. As one of the first places of worship in the North End, it established from the beginning a set style of worship and prominence in the community.

St. Luke's has always been a ritualistic church and a trend-setter in the renewal of services and its approach to Anglo-Catholic worship. Even in the early days of the 20th century, the rector was celibate, the liturgical colours changed with the seasons, all saints' days were observed, and a fasting communion was favoured.