With the win over Belgian 27th seed Mertens, Swiatek became the first player to reach the last 16 of a WTA 1000 event in 25 consecutive appearances.
Swiatek built a seemingly comfortable 5-2 lead in the first set but Mertens managed to claw back to 5-5 before the Pole ran away with the tiebreaker and breezed through the second frame.
"I'm happy that I got my level up in the tiebreaker to close it in two sets. Also in the second set I felt like I was playing good, big confidence," said Swiatek. "Yeah, overall I'm happy with the performance and how I worked through some issues."
Up next for Swiatek will be a clash with Ukrainian 22nd seed Elina Svitolina, a 6-2, 3-6, 6-2 winner over Czech 15th seed Karolina Muchova.
Svitolina, who arrived in Miami fresh off a quarter-final run at Indian Wells where she lost to eventual champion Mirra Andreeva, is now into the last 16 in Miami for the fifth time in her career.
In other early action, Australian Open champion Madison Keys, the American fifth seed, faced Filipino wildcard Alexandra Eala on Grandstand with the winner due to face Spanish 10th seed Paula Badosa, a 6-3, 7-6(3) winner over Dane Clara Tauson.
For 19-year-old Eala, it was another breakthrough performance, beating the American fifth seed 6-4, 6-2 and extending her dream run in Miami where she has now toppled two Grand Slam champions having beaten 2017 French Open winner Jelena Ostapenko in the second round.
Eala, who has trained at Rafa Nadal's academy in Mallorca since she was 13, required a medical timeout for what appeared to be a leg injury but was a force from the baseline against Keys, who reached the Indian Wells semi-final last week.
On the men's side, Bulgarian 14th seed Dimitrov, who lost to Italy's Jannik Sinner in last year's final, came back from one set down to secure a 6-7(3), 6-4, 7-5 victory over Russian Khachanov and set up a clash against either Belgian David Goffin or American Brandon Nakashima.
Six-time champion Novak Djokovic will cap the day session on Stadium Court when the Serbian fourth seed faces Argentine lucky loser Camilo Ugo Carabelli in a third-round match.
A win for Djokovic would give him 411 ATP Masters 1000 match wins, which would move him ahead of Rafa Nadal and into top spot on the all-time list.
