Calombaris went to Mazenod College in Mulgrave and studied at Box Hill Institute of TAFE. He won the Bon Land scholarship in 1999 while an apprentice.
He also entered the Bocuse d'Or culinary grand prix in Lyon, France, achieving a best result ever for an Australian representative.
He spent two years working at Reserve, in Melbourne’s Federation Square where, at the age of 24, he won Young Chef of the Year, Best New Restaurant and two chef's hats in The Age Good Food Guide. In 2004, the Global Food and Wine Magazine voted him as one of the Top 40 chefs of influence in the world. In 2006 Calombaris opened his own restaurant in Melbourne, The Press Club designed by renowned restaurant architects Mills Gorman. In 2008, he opened two other restaurants in Melbourne, Maha Bar and Grill (with chef Shane Delia) and Hellenic Republic (with chef Travis McAuley) both in collaboration with Mills Gorman. Also in 2008, he opened his first international restaurant, The Belvedere Club, in a hotel on the Greek island of Mykonos. In December 2010 Calombaris teamed up again with Mills Gorman to open P M 24 with culinary legend Philippe Mouchel. In 2011 he opened St Katherine's in Kew, again with Shane Delia and Mills Gorman. In January 2012 he opened Mama Baba located in South Yarra, Melbourne. According to his interview with Q Weekend 13-14 June, he is opening a new Greek restaurant (with something different), in Sydney at the end of 2015 or beginning of 2016.
Calombaris has published five cookbooks: The Press Club, Hellenic Republic: Greek Cooking from The Hellenic Heart, Your Place or Mine, Cook With Us with MasterChef Australia co-judge, Gary Mehigan and Georgie Porgie.
He appears in Who's Who in Australia 2011 edition and appeared at the 2011 Good Food & Wine Show.
In January 2012, he criticised the federal government's Fair Work Act for instituting high penalty rates paid to restaurant staff, which he claimed were uneconomical for small businesses. He complained that some of his restaurants were unprofitable on a Sunday because he was required to pay staff up to $40 an hour. He is quoted to have said "The problem is that wages on public holidays and weekends greatly exceed the opportunity for profit. And it's not like they've had to go to uni for 15 years".
On Mother's Day 2014, Hellenic Republic was forced to close for 24 hours after about 90 patrons complained of vomiting, diarrhoea and stomach cramps. A subsequent investigation by the Victorian Department of Health determined that a staff member was most likely responsible for an infection of norovirus. One customer is seeking damages for the injuries which he claims were suffered due to negligence and breach of contract.
In 2015, the Fair Work Ombudsman alerted Calombaris' MAdE Establishment Group to a problem with their payroll system, which had resulted in the mispayment of one staff member. Following this incident, the chief executive of MAdE Establishment, Troy McDonagh, commissioned an independent review into MAdE Establishment's payroll systems. In January 2017 this review discovered a number of payment discrepancies, which had resulted in some staff being underpaid, up to $2.6 million, while others had been overpaid. In April 2017, following this discovery, MAdE Establishment took steps to rectify the issue, voluntarily reimbursing the underpaid staff members at the highest overtime rate. In a personal statement, Calombaris said he was 'devastated' by the situation, and that correcting the underpayment was their 'highest priority.'
In May 2017, Calombaris was charged with common assault after making physical contact with a 19-year-old at Allianz Stadium during the 2017 A-League Grand Final. Video footage had shown Calombaris shoving the teenager who had heckled him over underpaying his staff. Calombaris said that he was offended after the spectator was "yelling out abusive and derogatory comments" towards his family. The victim denied the claim that the heckling was directed at the chef's family. Calombaris later apologised in a statement over his actions, saying "I regret the way in which I reacted, I am disappointed that I let it get to me, and I sincerely apologise for offending anyone." Calombaris was due to appear at the Downing Centre Local Court on 29 June 2017. However, he didn't appear at court on the date with the case then adjourned to August 10th, 2017. On August 17th, Brendan Green, a barrister on behalf of Calombaris, who was not present at the court, entered a guilty plea, with the case to be adjourned for sentence on September 8th, 2017.
Calombaris and partner Natalie Tricarico have a son born on 28 July 2011 and a daughter.
Calombaris has banned his children from eating food from fast food restaurants. Instead, he sends his son to birthday parties with a healthy packed lunch.
Calombaris is a Melbourne Victory supporter. He was the No.1 ticket holder for the 2012–13 season.