Victoria reported 64 new cases on Tuesday, taking the total number of cases in the state to 2,159.
Mr Andrews said the number of cases was “unacceptably high” and something that “poses a real threat to all of us”.
“We know that suburban lockdowns, stay-at-home orders are a series of restrictions that work,” he told reporters.
“We have all been through that journey, we have all been through that process and we know that at the end of that process we are then able to begin the process of opening up.”
Lockdown covers 10 postcodes
The lockdown applies to 10 postcodes in western and northern Melbourne: 3012, 3021, 3032, 3038, 3042, 3046, 3047, 3055, 3060 and 3064.
More than 300,000 people could be affected by the lockdown, according to Australian Bureau of Statistics population figures for each of the 10 areas.
Mr Andrews said police patrols would be conducted in these postcodes to ensure people were complying with the new orders.
"You shouldn’t be going into those postcodes over the next four weeks unless it is for work, and only for work that you have to do in person," he said.
"We have to limit the number of people who are going in and out of these postcodes and sadly we have to ensure that residents and families within these postcodes do not leave their home other than for those four permitted reasons, and again, only when they need to."
Victoria asks PM to divert flights
Mr Andrews on Tuesday said he had asked Prime Minister Scott Morrison to divert international flights away from Melbourne for the next two weeks, reducing the burden of returning travellers on Melbourne's quarantine arrangements.
"I will have conversations with other state leaders to explain that and to thank them in advance of the extra load that they will carry," he said.
Mr Andrews said a significant number of recent cases in northern Melbourne were linked to hotel staff members breaching quarantine procedures.
"That is unacceptable to me," he told reporters.
"I’m sure that will be unacceptable certainly to all of those who will be impacted by the restrictions that we have had to reimpose."
Of the new cases reported on Tuesday, six are part of the Stamford Plaza outbreak and were already in quarantine.
There are two new cases linked to Albanvale Primary School and two staff at a delivery service centre, StarTrack in Tullamarine, have tested positive to the virus. Both StarTrack employees worked while infectious and contact tracing is underway.
Five childcare centres will also undergo a deep clean after positive cases were identified there.
Four previous cases have been reclassified, so the total number of cases in the state has risen by 60 to 2,159.
Mr Morrison on Tuesday threw his support behind the lockdown of Melbourne suburbs.
The prime minister has also offered Commonwealth resources to secure the 10 hotspots.
"If indeed a full local lockdown is required in those hotspots, then that's the decision the premier will take," Mr Morrison said.
"And they'll take that decision with the full support and backing through resources from the Commonwealth government, as well as from other states and territories where that is necessary."
Deputy federal chief medical officer Michael Kidd has backed the decision to lock down hotspots.
“The actions being taken by the Victorian government will save lives,” he told reporters in Canberra.
People in Australia must stay at least 1.5 metres away from others. Check your state’s restrictions on gathering limits.
Testing for coronavirus is now widely available across Australia. If you are experiencing cold or flu symptoms, arrange a test by calling your doctor or contact the Coronavirus Health Information Hotline on 1800 020 080.
The federal government's coronavirus tracing app COVIDSafe is available for download from your phone's app store.
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Additional reporting by AAP.