Halep raced into a 5-0 lead in the opening set, breaking the defending champion three times and also saved three break points at 0-40 down in the fourth game.
The Romanian, who even shook off a hard fall in the second game, was at her aggressive and disciplined best while Pliskova looked sluggish with her on-court movement, failing to hit a single winner as she was bagelled in 20 minutes.
The limited number of fans allowed into Foro Italico's centre court urged Pliskova to make it a contest, applauding the rare points she got on the score board, and it seemed to work as the second set started with the pair breaking each other.
However, Pliskova was clearly struggling with an injury and despite receiving some treatment between sets on her lower back and leg, the Czech opted to retire to give Halep her first title in Rome.
"I know that's not the way how Karolina wanted to finish the tournament and the final," Halep said at the trophy presentation ceremony. "Good luck in the French Open, hopefully we will meet again there in the final.
"Finally, after two finals I could win this title. I love this tournament and I'm really happy that I have this beautiful trophy in my hands now."
Halep clinched her third consecutive title of the year after wins in Dubai before the coronavirus hiatus and Prague last month.
Halep, who chose to skip the hardcourt swing in the United States to practice on clay, will head to Roland Garros as one of the firm favourites with world No. 1 Ash Barty and U.S. Open champion Naomi Osaka both skipping the tournament this year.