Hundreds of cases have been reported across three states and a territory, with a dip in vaccination rates blamed for the spread of the generally rare respiratory disease.
Anthony Albanese urged people in the outbreak areas to get vaccinated.
"That is the most important thing that people can do," he told reporters.
"The government's taking it seriously."
There were 226 recorded diphtheria cases in the Northern Territory, Queensland, South Australia and Western Australia on Wednesday, up from 223 on Tuesday.
Federal Health Minister Mark Butler said the current outbreak was about 30 times greater than the average number of diphtheria cases recorded nationally over the past five years.
"It is a very, very concerning outbreak," he said.
The majority of new cases are respiratory diphtheria, which starts with flu-like symptoms, but can block airways and lead to suffocation.
About 25 per cent of cases are being hospitalised.Â
"This is obviously a deep concern for people who are exposed to this disease," Mr Butler said.
"(It's) also starting to place pressure on hospital systems in the NT."
Commonwealth health experts are working with the Northern Territory government, where 133 cases have been recorded.
Mr Butler said the federal government hoped to finalise a support package focused on vaccination later on Wednesday.
Authorities have also urged people to check they and their families are up to date with their vaccinations.
"When vaccination rates fall, serious diseases, which we had largely eliminated, can make a comeback," Australian Medical Association president Danielle McMullen said.
"We are seeing that risk play out with diphtheria."
Almost all the cases have involved Indigenous Australians, prompting health authorities to work with Aboriginal agencies to try to curb the outbreak, including the provision of vaccines.
WA Health Minister Meredith Hammat said the outbreak, which grew by three cases in the state from 79 to 82 overnight, was centred in the Kimberley region.
"We are taking the outbreak in the community very seriously," she said.
Public health officials are on the ground conducting contact tracing in the areas where cases have been recorded.
"We're doing everything we can to, in fact, not just limit it, but bring it to an end."
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