The world No. 1 raced through the first set but lost the second in a thrilling tie-break before recovering her composure to win the decider.
Barty is the first Australian woman to win the singles title since her idol Evonne Goolagong Cawley won it in 1980.
Pliskova, who was competing in just her second grand slam final, took too long to settle into the match and was made to pay for her early form despite improving in the more competitive second and third sets.
“I have to genuinely thank every single person in this stadium. You have made my dream so special, thank you so much,” Barty said during her on-court interview.
“It was an exceptional match right from the start, I knew I had to bring my very best level. I was really proud of myself with the way I was able to reset and just keep going.”
For the first time since 1977, both women were making their debut appearance in a Wimbledon final but one dealt with it much better than the other.
Pliskova started the match very nervous and Barty, with the superior experience, never really had to shift out of first gear during the opening exchanges.
The Czech player’s serve is usually her most potent weapon but even that abandoned her in the early stages — it took her until the third game before she even won a point.
The first set was over in a blur and there was seemingly no change at the start of the second with Barty going a break up once again.
But, with the match seemingly sliding away from Pliskova, she finally found her rhythm and broke back to make it 3-3.
It was like a different player had taken to the court, with Pliskova slamming aces and pushing Barty to her limits.
But the Australian looked equal to her opponent’s efforts and had the chance to serve for the championship, only to scupper the opportunity and lose in the resulting tie-break.
The decisive set was more like the final that many had expected, with both players demanding the very best out of each other.
Barty’s class eventually shone through as she recovered from a disappointing second set to win the decider in more comfortable fashion.
“She was playing an incredible tournament and incredible match today,” an emotional Pliskova said during her on-court interview.
“It wasn’t easy to close the second set, I was fighting to make it difficult for her but I think she really played very well so congratulations to her.”
It’s been an incredible journey to her first Wimbledon title for Barty.
Having enjoyed a stellar junior career, she took a break from tennis in 2014, later saying that the sport had become “robotic” and that she was a “victim of my own success.”
She turned to cricket and earned a contract as an all-rounder with Brisbane Heat back in Australia, before returning to tennis in 2016.
She went on to win her first grand slam at the French Open in 2019 before taking another break from the sport during the Covid-19 pandemic.