In a retrospective cohort study using SEER 8 data, researchers analyzed 3.36 million US cancer survivors diagnosed between 1975 and 2019 and identified 510,340 subsequent primary cancers (SPCs) over 29.5 million person-years. SPC incidence increased with age at initial diagnosis and declined modestly over calendar periods overall, but patterns varied by sex, cancer type, and birth cohort. Risk peaked among mid-20th-century birth cohorts and declined in more recent cohorts, except among female lung cancer survivors and male bladder cancer survivors, where incidence continued to rise. Survivors diagnosed at older ages also experienced persistent or increasing SPC risk despite overall declines.