Ukrainian Svitolina fought back from a set down to knock out second seed Elena Rybakina 2-6, 6-4, 6-4.
Polish fourth seed Swiatek followed up her emphatic win over Naomi Osaka in the previous round with yet another one-sided victory.
Against Pegula, she raced to a 5-0 lead before the American managed to win a game.
Swiatek never loosened her grip on the match, conceding three games overall.
The six-time Grand Slam champion finished with 15 winners compared to Pegula's six.
The victory marks Swiatek's first win over a top-10 opponent this year and continues an encouraging upswing after she began working last month with Francisco Roig, the former coach of her idol Rafa Nadal.
"I feel much better," Swiatek said. "I have a lot of confidence in my shots. I used that from the beginning of the match today and kept putting pressure on Jessie, so I'm really happy with how I played."
A title in Rome would come as a timely lift for the 24-year-old ahead of the French Open, where the main draw gets underway on May 24th.
Swiatek had been forced to retire from her previous tournament, the Madrid Open, in the round of 32 due to illness, leaving the court in tears.
Her path has also opened up significantly in Rome. With world number one Aryna Sabalenka knocked out in the third round by Romania's Sorana Cirstea, Swiatek has a renewed opportunity to end a claycourt title drought stretching back to her 2024 French Open triumph.
She is targeting a fifth title at Roland Garros.
Ukrainian seventh seed Svitolina fended off 16 break points as she squeezed past Australian Open champion Rybakina in a marathon evening match lasting nearly two and a half hours.
She reached the Rome semi-final for the first time since winning the title in 2018.
Sorana Cirstea will face two-time major winner Coco Gauff in the other semi-final.