Third seed Osaka had too much power for Brady as the Japanese star won 6-4 6-3 on Rod Laver Arena, adding to her Australian Open title of 2019 and pair of US Open titles from 2018 and 2020.
Brady, seeded 22nd and making a maiden appearance in a Grand Slam final, battled well in the first set and also threatened a resurgence in the second, but was ultimately undone by the power of her rival.
Osaka will rise to number two in the world rankings with her victory, still behind Australia’s Ash Barty, but on hard courts the Japanese star is unquestionably the planet’s unrivalled queen.
With talk of American great Serena Williams retiring after her tearful exit at the hands of Osaka in the semifinal this year in Melbourne, the 23-year-old’s triumph will also further establish her claim as the heir to Williams’ crown as the sport’s biggest female star.
Brady, 25, had been one of the stories of the tournament, being forced into a two-week hard quarantine on arrival in Melbourne when a fellow plane passenger tested positive for Covid-19.
That did not hinder her on a run to her first Major final, and she played her part in an entertaining match with Osaka before ultimately being outgunned.
The first set was tightest in front of a crowd of just under 7,500 fans on Rod Laver Arena as Osaka and Brady exchanged breaks of serve early on, with both having further opportunities to edge ahead.
But more experienced on the biggest stage, it was Osaka who made the crucial breakthrough – with some fortune – as Brady served to stay in the set.
The Japanese star saw a desperate backhand from out wide sail back over the net and land on the line, giving herself set point, before Brady then came forward only to find the net.
The second set was more straightforward for Osaka as she looked visibly more in control, breaking Brady twice to race into a 4-0 lead.
Although Brady roused herself to retrieve one of those breaks, Osaka duly responded, serving out the match in style to once again get her hands on the famous Daphne Akhurst Memorial Cup.
The victory means Osaka has won each of her first four appearances in Grand Slam singles finals – the first woman to do so since Monica Seles back in 1991.
She also becomes the first player, male or female, to win a fourth Grand Slam singles title since Russia’s Maria Sharapova did so at the 2012 French Open.
With those four titles in the bag, Osaka will be fancied to add to that haul considerably in the years to come after laying down yet another impressive marker on the hard courts.