The street was named for Sir Thomas Makdougall Brisbane, the sixth Governor of New South Wales.

The southern side of this section is part of a heritage precinct featuring typical forms of early housing.

[3] St Mary's Cathedral precinct is located at the corner of Brisbane and Harrington Streets.

[4] As an early named street in Hobart, it was the location of a number of significant activities and buildings in the colonial era.

[12] In 2018, a book of the churches in colonial Hobart identified the congregational buildings as surviving through to contemporary times.

[16] A memorial plaque, commemorating Reverend Frederick Miller, the first independent minister in the Australian colonies, and the founder of the Congregational church in Hobart, is located at 73 Brisbane Street.

[22] Other businesses on the street in the 1920's and 1930's included Absalom's Motor Garage,[23] and Tasmanian Corrugated Paper.