The prevalence of Helicobacter pylori (H. pylori) has decreased during several decades due to improvements in the sanitary environment in Japan. Consequently, a relative increase in the incidence of H. pylori-uninfected gastric cancer is expected. We analyzed the trends in H. pylori-uninfected gastric cancer. Two hundred fifty-eight patients with gastric cancer were retrospectively analyzed. The study was divided into four periods: 2008–2011 (first period), 2012–2014 (second period), 2015–2017 (third period), and 2018–2021 (fourth period). The status of H. pylori infection was divided into four categories: uninfected, successful eradication, spontaneous eradication, and persistent infection. Gastric mucosal atrophy was divided into six grades according to the Kimura–Takemoto classification. The proportion of H. pylori infections significantly changed over the study period (p = 0.007). In particular, the rate of H. pylori-uninfected gastric cancer tended to increase over time (0%, 2.9%, 4.9%, and 13.4% in the first, second, third, and fourth periods, respectively; p = 0.0013). The rate of no atrophy (C-0) in gastric cancer tended to increase over time (0%, 2.9%, 4.9%, and 11.0% in the first, second, third, and fourth periods, respectively; p = 0.0046). In conclusion, the rate of H. pylori-uninfected gastric cancer without gastric atrophy tended to increase over time.