The first Christian worship service in Melbourne was led by Henry Reed,[2] a businessman and Wesleyan lay preacher from Launceston, Tasmania.

The first service by an ordained Christian minister in Melbourne was led by Joseph Orton,[3] Wesleyan Superintendent of Tasmania, on 24 April 1836.

One of these was Mrs Varcoe, who established Livingstone House, a home for homeless boys in Drummond St, Carlton.

In 1893, during the acute depression which followed the bank crash of 1891, Alexander Robert Edgar was appointed as minister, with an expectation that he would develop a city mission and be its first Superintendent.

Edgar also began the "Pleasant Sunday Afternoon", where major speakers would speak about important public questions.

In the 1920s the Princess Mary Club, accommodation for single women working in the city was added, and in the 1930s, the Nicholas Hall.

In 2000, both the Congregation and the Mission Board became polarised over proposals to establish a primary care health facility in the grounds, which would have included the option of supervised drug injection.

This participation has been encouraged by the previous ministers, Jason Kioa and the late Rev Dr Douglas Miller.

The 1920s Princess Mary Club was controversially[9] demolished, and a large office building rose up along the east edge of the site, partly overhanging the retained Manse.

The grounds were landscaped and opened up to public use, and all the historic buildings including the church were restored, funded by Charter Hall as part of the deal that will also see a substantial rent paid for the office block on a 125 year lease.

The site was developed as a complex of related buildings, including a School House to the rear and a Manse/ Parsonage to the east, both also in Gothic bluestone, and designed by Reed.

The rear yard contains an olive tree planted in 1875 (this has long been thought to be from a cutting brought to Melbourne from Jerusalem in 1839, but there is no evidence to support this claim[12]).

[11] The Princess Mary Club was built on Lonsdale Street to the east of the church to provide accommodation for young women starting study or a career in the city, and was opened in 1926, but closed in the 1980s and demolished in 2017.