Romanian Halep, twice a runner-up at Roland Garros, started slowly but once she found her groove, there was nothing the 16th seed could do to avoid a one-sided defeat.
Halep won the last nine games on Court Philippe Chatrier to set up a meeting with either German Angelique Kerber or local favourite Caroline Garcia.
Mertens entered the tournament having won two second-tier events on clay including 16 wins and one defeat, albeit against Halep last month in Madrid when she was comprehensively beaten.
The story was the same on Monday as Halep, a French Open finalist in 2014 and 2017, broke for 2-1 in the opening set and never looked back as she outmanoeuvred Mertens, who was sent chasing the ball all over the court.
The Belgian pulled a break back in the second set but then trailed 5-0 as the top seed punched a ticket for the last eight when Mertens served a double fault on the first match point.
"It was not that easy, she is a tough opponent," said Halep, who is chasing her maiden Grand Slam title.
"I was a bit nervous at the start of the match but I played my best match here at Roland Garros.
"I need to be more aggressive and try to finish the points because I don't hit so many winners."
(Reporting by Julien Pretot; Editing by Ken Ferris)
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