Second seed Sabalenka needed an hour and 13 minutes to see off Ostapenko and improve her record against her Latvian opponent to three wins and no defeats.
In the last four crowd favourite Sabalenka will face the winner of two-time Australian Open champion Victoria Azarenka and Danielle Collins, this year's Miami Open winner, who face off later on centre court.
"With this amazing atmosphere and with this amazing support... that's why I'm super motivated here and that's why I always say that this is the dream tournament for me to win," said Sabalenka.
"I really enjoy playing here so I don't have to think about being focused... I'm just here enjoying it and doing everything I can to win every point I play no matter what the score. I guess that's the key."
The 26-year-old could get a rematch of the Madrid final which she lost in dramatic fashion to world number one Iga Swiatek earlier this month.
And Sabalenka, who has won the two most recent Australian Opens, was in a different class to Ostapenko who could do nothing in the face of some punishing hitting.
Rome is the first time since the 2013 French Open that the top three women have reached the last four of a WTA event of 250 level or higher, with Swiatek and world number three Coco Gauff in the other semi-final.
Following Sabalenka will be Alejandro Tabilo whose fairytale run in the men's tournament continues against China's unseeded Zhang Zhizhen for a place in the semi-finals.
Tabilo knocked out six-time Rome champion Novak Djokovic on Sunday and as the 29th seed will be favourite to set up a last four clash with either world number five Alexander Zverev or Taylor Fritz who play the day's final match.
Zverev, who won the Rome title in 2017, is the highest ranked man left in the event after Daniil Medvedev's elimination on Tuesday.
As well as Novak Djokovic's exit, Italian world number two Jannik Sinner and third-ranked Carlos Alcaraz both dropped out injured before the tournament.
Holger Rune, who lost last year's final to Medvedev, Madrid champion Andrey Rublev -- ranked sixth in the world -- and beaten finalist Felix Auger-Aliassime have also been eliminated.
