The Japanese player 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 her next match, she will face either world No. 2 Elena Rybakina of Kazakhstan or Yuliya Starodubtseva of Ukraine, who is ranked 58th.
Osaka won the US Open in both 2018 and 2020. She is currently ranked 13th in the world.
