The world No. 1 covered the first set but lost the second in a thrilling tie-break before regaining her composure to win the deciding match.
Barty is the first Australian to win the singles title since her idol Evonne Goolagong Cawley won it in 1980.
Pliskova, who was only making her second Grand Slam final, took too long to settle into the game and had to pay for her early form despite improving in the more competitive second and third sets.
“I have to sincerely thank everyone at this stadium. You made my dream so special, thank you very much,” Barty said during his on-pitch interview.
“It was an exceptional game from the start, I knew I had to bring my best level. I was really proud of myself with the way I was able to reset and continue.”
For the first time since 1977, the two women made their first appearance in a Wimbledon final, but one fared much better than the other.
Pliskova started the game very nervous and Barty, with the superior experience, never really had to step out of first gear in the first rallies.
The Czech player’s serve is usually her strongest weapon, but even that abandoned her early on – it took her until game three before she even earned a point.
The first set ended in a blur and there was apparently no change at the start of the second with Barty breaking up once again.
But, with the game appearing to move away from Pliskova, she finally found her rhythm and stepped back to bring the score to 3-3.
It was as if another player had stepped onto the pitch, with Pliskova slamming aces and pushing Barty to his limits.
But the Australian seemed equal to her opponent’s efforts and was fortunate enough to serve for the championship, only to spoil the opportunity and lose in the resulting tie-break.
The deciding set was more like the final than many expected, with both players demanding the best of each other.
Barty’s class finally shone as they recovered from a disappointing second set to win the deciding match in a more comfortable way.
“She was playing an amazing tournament and an amazing game today,” said a moved Pliskova during her interview on the pitch.
“It was not easy to close the second set, I was fighting to make it difficult for her but I think she played really really well, so congratulations to her.”
It was an incredible journey to his first Wimbledon title for Barty.
After enjoying a successful junior career, she took a hiatus from tennis in 2014, later claiming that the sport had become “robotic” and that she was “a victim of my own success”.
She turned to cricket and got a contract as an all-rounder with Brisbane Heat in Australia, before returning to tennis in 2016.
She went on to win her first grand slam at Roland Garros in 2019 before taking another break from sports during the Covid-19 pandemic.
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