Nicholson Street was built in 1854 to provide a road from Melbourne to the stone quarries of Brunswick East.

[2] In 2013, Public Transport Victoria proposed changed traffic conditions to much of the street by enforcing dedicated tram lanes along the length of Route 96, which would result in the removal of all on-street parking in favour of through traffic lanes and less delays for trams.

Several Melbourne landmarks are located on Nicholson Street, including Parliament House and the Princess Theatre at its southern terminus.

Just to the north lie the Royal Exhibition Building and the Melbourne Museum, both in Carlton Gardens, and St Vincent's Hospital.

[3] Further north in Brunswick East, at the corner of Blyth Street, Melbourne alternative radio station 3RRR makes its home.