Halep came through a testing quarter-final clash with resurgent former world No 1 Angelique Kerber, coming from behind to win 6-7, 6-3, 6-2. She had her second shot at the title in 2017 but lost again to the Latvian revelation Jelena Ostapenko.
10th-seeded Sloane Stephens had never made it past the fourth round in Paris until now.
The former world number one drilled a backhand victor down the line to hold again in the next game, the 28th seed clenching her fist as she walked to the chair.
Muguruza is 3-0 in career grand slam semifinal matches.
The clay courts of Roland Garros host the second Grand Slam of the season.
Service breaks were exchanged at the start of the second set but Muguruza is a far steelier player than four years ago and Sharapova did not get a sniff in the next five games as the Spaniard reached her fourth Grand Slam semi-final.
"So doesn't matter who is playing against". "I've had issues with the right pectoral muscle to the point where I can't serve", said the 36-year-old after withdrawing from the match.
"I think there is a lot of autobiographies out in the world, especially in the sporting world, that don't necessarily speak about whether they were rivals or someone they competed against", Sharapova said. At the Miami Open in March, she won the title, beating four major champions in a row.
Israeli army kills Palestinian near fence in southern Gaza
The 21-year-old paramedic was reportedly shot in the chest while trying to medically assist injured protesters near the border. Since nonviolent protests began at the end of March, Israeli soldiers have killed at least 119 people, including 14 children.
"So tomorrow is going to be a big challenge for me".
It was not enough, however, as Wimbledon champion Muguruza bulldozed her way through the rest of the set to secure her place in the semi-finals.
"I think I played one of my best matches on clay", Halep told reporters after Thursday's win.
After her third-round win against Julia Goerges, Williams charged at Sharapova's book, questioning why it wasn't truthful - at least to her - and why Sharapova was so obsessed with her as a subject. Halep then seized her chance, moving 0-40 ahead and then raising her arms in triumph as Muguruza blazed a backhand long. I'm not ever going to try to be a person that isn't nice, so that feels more authentic to me and, you know, I think I'm still doing okay.
Stephens put a higher percentage of first serves into play (76.2 percent) than anyone in the draw other than her first-round victim, Arantxa Rus.
"I think it would be unusual for me not to include someone that I have competed against for so many years", said the 31-year-old.
That became 4-2 before Halep broke back for 4-4 and then held serve in a 14-minute game which went to a seventh deuce and saw Muguruza blow three break points.
"I don't know that I would call the hard road", Murray said. I was a little bit upset of what I have played those points. As she told the press after her quarterfinal win, "There were times when I had to go back and hit a higher ball, where maybe before I would have tried to hit a line-drive victor".