Brien Lane leads north from Bourke to Little Bourke streets, between Russell and Exhibition streets. It was named in 1872, possibly after butcher Joseph Brien. In the 1890s, Brien Lane was connected to Healey Lane, now Coverlid Place, and Commercial Lane, now Croft Alley, and still contained the 'remains of sheds'. Between 1890 and 1920, it was also home to the Gospel Mission Hall.
In 2008, Brien Lane hosted a cinema complex at the Bourke Street end and two Chinese restaurants towards Chinatown. In 2002, it also displayed a City of Melbourne Laneway Commission by Louisa Bufardeci. The commission was called 'There are a few facts I think you ought to know', and consisted of a colourful bar-graph mural painted directly onto the road surface and illustrating demographic and statistical information relevant to Melbourne.