The Russian, back on the Paris clay having missed the last two tournaments due to a doping ban, was swept aside 6-2 6-1 by the Spanish third seed.
"I was up against a great player so I had make sure I brought my best tennis".
Sharapova, who missed the 2016 tournament because of a doping ban and a year ago after she was refused a wild card, was broken six times, committed 27 unforced errors and won just five points on her own serve in the second set.
Two-time victor Sharapova made her return to Roland Garros after three years, and advanced to her 25th Grand Slam quarter-final after her arch rival Serena Williams withdrew prior to their 22nd encounter.
Muguruza pounced on an error-plagued Sharapova start to lead 4-0 with a double break.
The signs were ominous when the five-time Grand Slam champion coughed up three nervy double-faults in the opening game.
Maria Sharapova's French Open comeback was ended in straight sets by ruthless Garbine Muguruza.
Contesting her first French Open since failing a drugs test at the 2016 Australian Open, 31-year-old Sharapova said it was now time to be realistic.
However, it was just a brief respite.
Muguruza conceded just three games to race past Sharapova in one hour and 10 minutes.
"To have had the victories that I have had, to have the results that I have, obviously moving a step in the right direction", said Sharapova, who had made the last eight in Madrid and semis in Rome in the run-up to Paris. "So I think that's why I won today", Halep said.
After making 30 unforced errors in the first set, which she lost 7-6 (2), Halep finally found the right rhythm to dictate points with deep groundstrokes and aggressive returns.
Kerber eventually prevailed in a tiebreak, but Halep came out all guns blazing in the second, firing baseline bullets at her opponent, who tried to cling on against the onslaught.
Halep secured an early break in the second and did not relinquish it despite some fierce pressure from two-time major victor Kerber, with one remarkable get at the net even prompting applause from the German.
"Well, I think it would be unusual for me not to include someone that I have competed against for so many years", she said, responding to Williams' barb that she was surprised to feature so frequently in the book.
"After the first set I just stayed strong and didn't give up". She says she rushed too much early.
"Not long after I heard Serena told a friend, who then told me, "I'll never lose to that little bitch again".
In Thursday's other semi-final, US Open champion Sloane Stephens will take on fellow American Madison Keys in a repeat of the 2017 final at Flushing Meadows.