The Japanese woman started by winning the first set (6–3), but then had to fight for victory after Mertens levelled at 1–1.
"It was a special moment when I felt like I put my whole heart into the court. I kept fighting for every point," Osaka said.
In the next match she will face world number two Elena Rybakina from Kazakhstan.
Osaka won the US Open in both 2018 and 2020. She is currently ranked 13th in the world.
