Abstract Purpose: Pembrolizumab demonstrated efficacy in PD-L1–positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (G/GEJ) cancer in the first-, second-, and third-line setting in KEYNOTE-062, KEYNOTE-061, and KEYNOTE-059, respectively. To better delineate the specificity of CPS as a predictor of clinical outcomes, we analyzed pembrolizumab efficacy in patients with CPS ≥ 10 in these trials. Patients and Methods: Included were patients with CPS ≥ 10 tumors from KEYNOTE-059 cohort 1 (pembrolizumab, n = 46; post hoc), KEYNOTE-061 (pembrolizumab, n = 53; chemotherapy, n = 55; post hoc), and KEYNOTE-062 (pembrolizumab, n = 92; chemotherapy, n = 90; primary). Efficacy outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Results: In KEYNOTE-059, median follow-up was 6 months, median OS was 8 months [95% confidence interval (CI), 5.8–11.1], ORR was 17%, and median (range) DOR was 21 months (3+ to 35+). In KEYNOTE-061, median follow-up was 9 months, median OS (pembrolizumab vs. chemotherapy) was 10 versus 8 months (HR, 0.64; 95% CI, 0.41–1.02), median PFS was 3 months versus 3 months (HR, 0.86; 95% CI, 0.56–1.33), ORR was 25% versus 9%, and median (range) DOR was not reached (4 to 26+ months) versus 7 months (3–7). In KEYNOTE-062, median follow-up was 11 months, median OS (pembrolizumab vs. chemotherapy) was 17 months versus 11 months (HR, 0.69; 95% CI, 0.49–0.97), median PFS was 3 months versus 6 months (HR, 1.09, 95% CI; 0.79–1.49), ORR was 25% versus 38%, and median (range) DOR was 19 months (1+ to 34+) versus 7 months (2+ to 30+). Conclusions: This comprehensive analysis showed consistent improvements toward more favorable clinical outcomes with pembrolizumab across lines of therapy in patients with CPS ≥ 10 G/GEJ cancer.