Victorian Health Minister Jenny Mikakos resigned from parliament on Saturday.
It came a day after Premier Daniel Andews pointed finger at her for hotel blunder.
Spread of COVID-19 cases from returned travelers to community led to outbreak.
Mr Andrews fronted the inquiry on Friday, contradicting Ms Mikakos' evidence.
Victorian Health Minister Jenny Mikakos has resigned from parliament, one day after Daniel Andrews pointed the finger at her over the state's quarantine hotel blunder.
Premier Andrews told an Inquiry that he regarded Ms Mikakos 'accountable for the program', which led to a surge in coronavirus cases and a statewide lockdown.
Less than 24 hours after the premier made his comments, Ms Mikakos handed in her resignation as both a minister and member of parliament.
Despite widespread calls for heads to roll over the handling of the hotel quarantine, Ms Mikakos is the first domino to fall.
On her way out the door she did not hesitate to take one final swipe at Mr Andrews, saying she too wanted to know who was responsible for the hotel disaster.
'I have never wanted to leave the job unfinished but in light of the Premier’s statement to the Board of the inquiry and the fact that there are elements in it that I strongly disagree with, I believe that I cannot continue to serve in his Cabinet,' Ms Mikakos said in a statement on Twitter.
'I am disappointed that my integrity has sought to be undermined.
'I have today written to the Governor of Victoria to resign my commissions as a Minister effective today. I will also be resigning from the Parliament.'
Pressure on Ms Mikakos mounted after her testimony to the inquiry on Thursday was conflicted by Mr Andrews' on Friday.
Ms Mikakos told the hearing that 'to the best of her recollection' she did not know private guards were enforcing the scheme until late May when the Rydges hotel suffered a coronavirus outbreak.
But a video of a press conference on 29 March - two days after the quarantine scheme was announced - shows Ms Mikakos standing alongside jobs minister Martin Pakula as he said: 'Passengers returning will now undergo mandatory two-week quarantine at those Melbourne hotels with security guards in place.'
In a written statement to the inquiry, Ms Mikakos wrote: 'I believe I first became aware of the use of private security guards... after the Rydges outbreak occurred in late May 2020.'
Speaking at the inquiry on Thursday she added: 'That's to the best of my recollection… because I would have had no reason to turn my mind to issues around security guards until we had that first case and the first outbreak at the Rydges hotel.'
Opposition MPs have accused Ms Mikakos of lying, including shadow housing minister Tim Smith who said she 'is a liar and must go'.
Asked if the video contradicts Ms Mikakos' evidence to the inquiry, her spokesman told it Australia: 'The Minister categorically denies that she has misled the Board in any way and has sought leave to provide information to the Board to that effect.'
On Friday Premier Daniel Andrews told the inquiry he regarded Ms Mikakos 'accountable' for the hotel quarantine program.
The virus escaped from hotel quarantine in late May and sparked the state's second wave which has seen more than 700 deaths.
The Victorian government has faced criticism for not accepting ADF troops and instead using private security guards, some of whom flouted social distancing rules and failed to properly wear PPE, witnesses told the inquiry.
Ms Mikakos said she was 'not part of the decision-making process' to use private security guards.
In August the inquiry heard the decision to use private guards was made in an Emergency Management Victoria meeting at 4.30pm on 27 March.
The state government agency, established in 2014, is led by top cop Andrew Crisp.
Victorian jobs department secretary Simon Phemister said his team was told to hire security firms to run the quarantine operation after that meeting.
Mr Paukula said his department was not responsible for the decision and questions about it need to be directed to Commissioner Crisp.
Mr Crisp told the meeting that private security would man the hotels without troops, the inquiry heard.
'At this stage… at this particular point in time, we certainly don't see the need for boots on the ground for this particular operation,' he told the meeting, according to a recording heard at the inquiry in August.
Despite the litany of criticisms aimed at the embattled state politician and her handling of the once-in-lifetime crisis, she tried to distance herself from blame.
'With the benefit of hindsight, there are clearly matters that my department should have briefed me on,' Ms Mikakos said in her resignation letter.
'Whether they would have changed the course of events only the Board and history can determine.
'For three months I had looked forward to learning who made the fateful decision to use security guards. Victorians deserve to know.'
But while Ms Mikakos acknowledged she is responsible for her department and that 'the buck stops with me'.
She also said 'it is not her responsibility alone' and does not believe her actions contributed to the second wave of cases which have ravaged the state.
'Since the start of the pandemic. I have worked every day with a single focus - to protect Victorians from an unprecedented global public health threat in our life-time,' Ms Mikakos said.
'It has been a responsibility for which I have felt only a sense of urgency and resolve.
'The sacrifice and suffering of Victorians is something that I feel deeply.'
While Liberal Party opposition MPs in Victoria will be pleased to see the Health Minister walk out on the job, Ms Mikakos has received a message of support from NSW Health Minister Brad Hazzard.
'Sorry to see Jenny Mikakos resign. She has worked tirelessly in this pandemic,' he posted to Twitter in an extraordinary showing of cross-party support.
'Premier Andrews assertion that the Health Minister was responsible for the Quarantine system lacks logic.
'How could a Health Minister direct Police to be involved?'
Step one: The first step came into effect at 11.59pm on September 13.
Step two: The second step will be implemented when Melbourne has 30-50 COVID-19 cases a day on average over the past 14 days. The aim is for this to come into place on September 28.
Step three: The move to step three will occur when there is a daily statewide average of five new cases over the past 14 days. The aim is for this to come into place on October 26.
Step four: The move to step four will come when there have been no new COVID-19 cases in the past 14 days. The aim is for this to come into place on November 23.
COVID Normal: After 28 days of no new COVID-19 cases, things will return to normal.
Step one - 11.59pm on September 13: now in effect
- Curfew has been eased to 9pm-5am
- People can still only leave home for the four reasons (shopping, exercise, work and care or medical attention)
- Public gatherings increased to two people, or a household, for a maximum of two hours
- Singles can have one nominated person to their home as part of the 'singles social bubble'
- Childcare and early educators to remain closed
- Schools will continue to learn remotely unless they have exemptions
- Adult education to continue to be done remotely, unless they have exemption
- Only go to work if you are in a permitted industry
- Cafes and restaurants will continue with take away only
- Retail businesses will remain open for essential shopping, with others only operating with click and collect
- Only one person per household can do the essential shopping
Step two - September 28:
- Public gatherings increase again to five people from a maximum of two households
- Childcare and early educators can re-open
- Schools to continue with remote learning, but Prep to Grade Two and Year 11 and Year 12 students will gradually return to class in Term 4
- There will be an increase to permitted workplaces
Step three - October 26:
- Curfew is no longer in place
- There are no restrictions on leaving home
- Public gatherings increase to 10 people together outdoors
- A 'household bubble' will be introduced, so five people from one house can visit another
- Remote learning to continue, but Grades 3 to Year 11 can gradually return to class
- Adult education to continue to be done remotely, but hands on classes will see a phased return to onsite
- Work from home is encouraged
- Up to 10 people can eat together at restaurants and cafes, with the majority of tables outdoor
- Retail shops to reopen, with hairdresses operating under safety measures but beauty stores to remain closed
- Real estate agents can conduct private inspections by appointment
- The one person per household limit on shopping is to be revoked
Step four - November 23:
- Public gatherings to increase to 50 people outdoors
- Up to 20 visitors can attend a home at any one time
- All adult education will return to onsite with safety measures in place
- Groups limited to 20 indoors and a maximum of 50 patrons per venue
- All retail stores to reopen, while real estate agents can operate with safety measures and by keeping a record of attendants
Step five - COVID normal:
- Public gatherings have no restriction
- There will also be no restriction on visitors to homes
- Phased return to onsite work for work from home workers
- Schools to reopen as normal
- Restrictions on hospitality removed, but venues to continue keeping records