It is a second title of 2025 for the 31-year-old, after her triumph at the Austin Open in March, and it is her first singles title on clay.
"Congrats to Sonya [Kenin] on an amazing week - you've been playing some good tennis this year," said Pegula in her post-match speech.
"You're always a tough opponent. I wish you nothing but the best for the rest of the clay season, to you and your team. I'm sure I'll be seeing you again very soon.
"Thanks to my team for always supporting - it's been a great week."Pegula will replace Coco Gauff as the US No. 1 after battling her way to the Charleston Open title on Sunday.
Thanks to her triumph at the WTA 500 event, she will rise back to her career-high of world No 3 on Monday - knocking Gauff down to world No. 4.
Pegula previously had the chance to return to world No 3 - and US No 1 - in the Miami Open final last weekend, though she was beaten by Aryna Sabalenka.
However, the 31-year-old has bounced back with an impressive run in Charleston, and will now hold a slender lead rankings lead over Gauff come Monday.
Pegula will sit on 6,101 points, with Gauff just 38 points behind on 6,063.
But, while the lead is currently narrow, Pegula holds a significant advantage looking ahead towards the rest of the clay season.
After reaching the semi-finals of the Charleston Open in 2024, she missed the rest of the clay swing due to injury.
Pegula has no ranking points to defend until the grass-court swing and, with significant events in Madrid and Rome to come before the French Open, she has an opportunity to earn significant points.
In comparison, Gauff has semi-final points to defend at both the Italian Open and Roland Garros, alongside further points in Madrid and at the Stuttgart Open.
Pegula could also turn her attention to challenging world No. 2 Iga Swiatek, and potentially move to a new career-high ranking.
The Pole is now only five points ahead of Pegula in the WTA Race to Riyadh and, having not reached a final this season, is under significant pressure heading into the clay swing.
While Pegula has no points to defend, Swiatek is defending 4,000 points as the reigning Madrid, Rome, and Roland Garros champion, alongside further semi-final points at the Stuttgart Open.
Swiatek currently holds 7,470 ranking points - only 1,369 more than Pegula will on Monday.
The WTA 500 event in Stuttgart is set to be the next event for both women, as well as for world No. 1 Sabalenka and 2023 US Open winner Gauff.
While there was disappointment for Kenin in Sunday's final, an impressive run to her 10th WTA singles final also sees her move up the rankings.
The former Australian Open champion is set to rise 10 spots to world No 34 on Monday, and is now well-placed to challenge for a French Open seeding.