The top-seeded and former Osaka titlist Stosur held off Thai qualifier Noppawan Lertcheewakarn 6-3, 3-6, 7-5 in 2 hours, 13 minutes on the hardcourts at Utsobo Tennis Center.
The Australian Stosur beat American Serena Williams in last month's U.S. Open final to capture her first-ever Grand Slam singles title. She won this Osaka event two years ago to secure her first-ever singles title on the WTA circuit.
Up next for Stosur in Osaka will be Japan's own Misaki Doi.
Four other seeds joined Stosur in the second round, as No. 3 German Angelique Kerber whipped Japanese wild card Kurumi Nara 6-2, 6-1 in 67 minutes; No. 4 Czech Petra Cetkovska doused long-time Japanese crowd favorite Kimiko Date- Krumm 6-2, 7-6 (7-2); No. 5 Aussie Jarmila Gajdosova dismantled Japanese wild card Aiko Nakamura 6-0, 6-1; and No. 6 Japanese Ayumi Morita got past China's Zhang Shuai 7-6 (7-3), 6-2. The 41-year-old Date-Krumm was last year's Osaka runner-up to Thailand's Tamarine Tanasugarn and was also the runner-up here back in 1993.
The 34-year-old Tanasugarn will face France's Mathilde Johansson in a second- rounder here on Wednesday.
This week's champion will take home $37,000.