Notable landmarks on William Street include the Queen Victoria Market, the Flagstaff Gardens, Immigration Museum, Supreme Court of Victoria, AMP Square, Australian Club and 140 William Street.

On 18 June 2007, a shooting incident occurred on the corner of Flinders Lane and William Street when an unknown man shot and killed a pedestrian and wounded two others.

[2] On 20 January 2017, a car was driven into pedestrians in the central business district of Melbourne, killing 5 and injuring over 20.

[4] Several buildings and structures on William Street are listed on the Victorian Heritage Register and/or classified by the National Trust of Australia.

Flagstaff railway station is situated on William Street.