Police have formed a cordon around the creature as they awaita snake catcher, with the unusual sight drawing a large crowd which has spilt onto Spencer St.
One southbound lane of Spencer St had to be closed.
City of Melbourne posted a photo of the snake on Twitter and urged people to avoid the area.
"We're currently trying to remove a snake who seems to be a little lost," the council wrote.
Metro Trains also urged passengers travelling to or from Southern Cross station to take extra precaution.
Please avoid the corner of Collins & Spencer streets. We’re currently trying to remove a snake who seems to be a little lost. pic.twitter.com/ujN3IU52uw