Osaka's big-match experience was telling against first-time finalist Brady, the former world No.1 reeling off six consecutive games after breaking at 4-4 in the first set to set the tone at Melbourne Park on Saturday.
Japanese star Osaka became the first woman since Monica Seles in the early 1990s to emerge victorious from the first four grand slam finals of her career, having boasted a perfect 3-0 record after success at the US Open (2018 and 2020) and Australian Open (2019).
Osaka, who fended off a pair of match points against Garbine Muguruza in the last 16 at Melbourne Park, also became the seventh woman to have won the Australian Open after saving match point, following in the footsteps of Seles (1991), Jennifer Capriati (2002), Serena Williams (2003 and 2005), Li Na (2014), Angelique Kerber (2016) and Caroline Wozniacki (2018).
Fans were treated to a topsy-turvy opening on Rod Laver Arena, in a rematch of the 2020 US Open semi-final, which Osaka won en route to her third Major title.
Osaka appeared to be on track for a commanding first set, cruising through the opening service game to love before breaking her opponent to love after a double-fault for a 3-1 lead.
Looking rushed in her maiden Major final as Osaka enjoyed the big stage, Brady wrestled the momentum after reclaiming the break, the No.22 seed starting to outhit the former in a fascinating baseline battle.
Some out of character misses and errors crept into Osaka's game – 15 in total in the opening set, she managed just 21 in total in her straight-sets win over Serena Williams in the semi-finals.
Full of confidence, Brady had a chance to break Osaka, who fended it off to move ahead 5-4 before the debutant crumbled.
In control at 40-15, Brady's position wilted as she was was caught off-guard by an Osaka return that caught the line and it got worse after firing a volley into the net to gift the No.3 seed the set.
For all of her hard work in an absorbing first set, Brady's hard work came undone early in the second, the fast-moving Osaka winning four consecutive games to close in on victory.
Brady managed to stop the rot by breaking back and clawing two consecutive games, however, it only delayed the inevitable as Osaka further cemented herself as the face of women's tennis.