She last won a Major at the 2017 Australian Open when she was four weeks pregnant.
The Serbian world number one and his Swiss opponent have won eight of the nine titles on the Rod Laver Arena since 2010, and 11 of the last 13 on the bright blue courts in central Melbourne.
Famously, Roger Federer won the men's singles last year and will be looking to make this his 100th tournament victory by winning again this year.
Bookmakers in Australia have installed Williams as a short-priced favorite for the title with her US Open conqueror Osaka - the first Japanese player to win a Grand Slam - next in the betting.
In her comeback year, she reached the finals of both Wimbledon and the US Open.
Serena Williams hopes that his Australian Open will allow her to match Margaret Court's record of 24 Grand Slam titles. He expects her to be in the title mix going forward.
The popular 21-year-old's US Open triumph was overshadowed by Serena Williams' tantrum in the final at Flushing Meadows but Osaka has the opportunity in Melbourne to demonstrate she can withstand the spotlight of being the new standard bearer for tennis in Japan, Asia and the next generation of women. Among those looking to halt Serena's charge: world number one Simona Halep, defending champion Caroline Wozniacki and US Open victor Naomi Osaka.
The tournament's top-seed and World's No. 1 Novak Djokovic of Serbia, who is the Australian Open six-time champion and aims this month for record-breaking 7th title, is facing a qualifier in the opening hurdle in Melbourne.
Williams missed her first chance to match Court when losing last year's Wimbledon final to Angelique Kerber, and said ahead of the Australian Open that she was taking nothing for granted.
"In general, it's about her offensive game", Rittner told Deutsche Welle of the three-time Grand Slam champion who lost an agonising, breathless semi-final 9-7 in the final set to Halep in Melbourne a year ago. But coming from Constanta [her home city], from nowhere, and becoming the best, is pretty huge for a Romanian, and for me as a person.
"I noticed she seems fitter, which is a scary thought. I enjoy Grand Slams the most", she said.
Australia Open is slated to be held from January 14 to 27 in Melbourne, Australia.
Murray, a five-time finalist at Melbourne Park, spent most of a year ago recuperating from hip surgery and looked rusty last week in Brisbane, but declared himself pain free.