Prime Minister Malcolm Turnbull said he had accepted Ms Ley's resignation on Friday.
Entitlements scandals have engulfed Australian politics in recent years.
Mr Turnbull has now pledged to set up an independent watchdog, based on the UK system, to oversee parliamentary expenses.
"Australians are entitled to expect that politicians spend taxpayers' money carefully, ensuring at all times that their work expenditure represents an efficient, effective and ethical use of public resources," he said.
"We should be as careful and as accountable with taxpayer money as we possibly can be."
In her resignation statement, Ms Ley maintained she had not broken any rules, "not just regarding entitlements but most importantly the ministerial code of conduct".
However, she said the saga had become a distraction for the government.
"Whilst I have attempted at all times to be meticulous with rules and standards, I accept community annoyance, even anger, with politicians' entitlements demands a response," she said on Friday.
Ms Ley faced pressure over separate trips to the Gold Coast, where she purchased the A$795,000 (Â£473,300; $585,200) investment property in 2015 and attended New Year's Eve parties in 2013 and 2014.
She described the apartment purchase as an "error of judgement" that was "neither planned nor anticipated".
Mr Turnbull said he believed Ms Ley's resignation was the "right judgement" and thanked her for her service.
He said the new expenses watchdog would ensure that politicians' claims were transparent to the public.
"I have to say I hate the term entitlements. These are work expenses," he said.
"The circumstances require us to be seen to be putting these matters plainlyâ€¦ so that people can be assured there is independent oversight."
The opposition Labor Party offered "in-principle" support for Mr Turnbull's reform.
"We're happy to work with him on work expenses for politicians," said acting Labor leader Penny Wong.
"I think the country and the people expect it."
The UK set up the Independent Parliamentary Standards Authority in 2010 in the wake of the MP expenses scandal.
Australian Health Minister Sussan Ley has resigned after using a taxpayer-funded trip to purchase an apartment on Queensland's Gold Coast.