The pizza chain has outlets in all other Australian capitals and has now bought out Melbourne chain Big Daddy's Pizza.
Domino's chief executive Don Meij said the first of Big Daddy's 16 stores would reopen as a Domino's outlet in two-and-a-half weeks.
The opening of Domino's stores in Shepparton, Ballarat and Bendigo sparked pizza wars, with local outlets dropping their prices to try to run the newcomer out of town.
Meij said prices were already very competitive in the Melbourne market and size did not guarantee success.
"The interesting thing about Melbourne, it's every guy on the corner who is the market leader - people own their territory where they operate," he said.
Domino's believes the market for pizza in Melbourne is growing, even though there are already 800 pizza outlets across the city.
Big Daddy's Pizza managing director Al Dannauoi, selling out for family and health reasons, said his chain had needed a big player to come along and make it grow.
"It is a sad moment in my career - there's (been) a lot of blood sweat and tears go into it," he said.
Domino's plans to take on many of Big Daddy's staff, but will also be looking for about 500 additional staff.
A spokeswoman for Melbourne pizza chain La Porchetta said that chain would not be changing anything to respond to Domino's arrival.
"Our focus is on the fresh ingredients and the authentic Italian cuisine at an affordable price targeted at the family and we won't be changing anything to adapt to the competitors that might be entering the market at this time," she said.