The duo played out an utterly compelling second-set tiebreak, with Pavlyuchenkova squandering a 6-3 lead and five set points as she fell at the quarter-final hurdle at the All England Club for a fourth time.
Three years after reaching the quarter-final stage at Wimbledon, Anisimova has gone one step further, and for the majority of the match, her game looked tailor-made for the grass.
Incredibly, the 13th seed failed to get through qualifying last year after dropping down the rankings, so this represents a meteoric turnaround for the massively talented American.
Following her victory, she was joined on court by her young nephew Jackson, who could be heard throughout.
"It was such a battle today. I was up in the second set and she started playing some unreal tennis," Anisimova told the crowd with Jackson by her side.
"I just kept fighting and that tiebreak was super stressful, but I'm just so happy I got it done. I'm happy to be in the semi-final for the first time, it's super special."
"It has been an extraordinary year for me with so many highs. I am enjoying every step of the way and, even in times like today, I keep reminding myself to enjoy the moment."
From the off, Anisimova struck the ball beautifully from the back of the court, with her signature backhand in glorious full flow, ending the match with 26 winners to Pavlyuchenkova's nine.
Pavlyuchenkova seemed to be no match for Anisimova for long periods, but found her level towards the end of the second set, but it proved to be too little, too late.
Anisimova now faces world number one Aryna Sabalenka in a tantalising semi-final clash, after the Belarusian edged past Laura Siegemund in three sets.
Interestingly, Anisimova leads the head-to-head with Sabalenka 5-3, and she will certainly go into the contest with confidence.
Pavlyuchenkova went into the quarter-final in the knowledge that she hadn't beaten Anisimova in their three meetings, and it was clear to see why at the very start.
The 23-year-old raced to a 4-0 lead against her Russian opponent before she finally got on the board in the fifth game of the match. However, Anisimova continued to crush the ball, breaking again to take the opening set 6-1 in just 27 minutes, despite her first serve percentage continuing to be an issue as it has been all tournament - landing just 53%.
Pavlyuchenkova put up far more of a fight in the second set, saving two break points in the fourth game after some uncharacteristic errors from Anisimova.
Anisimova then failed to serve out the match at 5-4, missing two set points in the process, as Pavluychenkova began to raise her level on the big points with some gutsy tennis. An incredible drop shot out of the blue looked to be the turning point, as the momentum slowly shifted.
The Doha champion started to cut a frustrated figure, slumping on her knees after missing several more opportunities to take the initiative, with her game falling away.
The tension was clear to see for both players in the tiebreak, but Anisimova produced some sublime tennis and showed great character to save several set points.
But finally, on the fourth time of asking, Anisimova sealed the win after a backhand into the net from Pavlyuchenkova, as she dropped to the floor in ecstasy.
She has now become the first woman born in the 2000s to reach a Wimbledon semi-final (2001), a feat that can be matched by Iga Swiatek (2001) and Mirra Andreeva (2007) tomorrow.