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Background and Objectives: Cancer incidence patterns in South Korea have shifted markedly over the past two decades, with notable increases among younger generations. Despite growing concern regarding early-onset cancer, comprehensive assessments of long-term age-, period-, and cohort-specific trends across multiple cancer types remain limited. This study examined nationwide cancer incidence trends from 2001 to 2020 using Joinpoint regression and age-period-cohort (APC) modeling. Materials and Methods: A population-based analysis was conducted using Korea Central Cancer Registry (KCCR) data, including all primary malignant tumors diagnosed from 2001 to 2020. Incidence rates were calculated by sex and 5-year age groups and standardized to the mid-2000 Korean population. Joinpoint regression estimated annual percent change (APC) and average annual percent change (AAPC), accounting for overdispersion and autocorrelation. Independent temporal effects were evaluated through APC modeling using overlapping 10-year birth cohorts, with the 1961 cohort as the reference. Results: Incidence increased for prostate, kidney, breast, and pancreatic cancers, while stomach, liver, lung, and biliary cancers showed continued declines. Colon cancer rose until 2011 and decreased thereafter. More recent birth cohorts exhibited higher risks for prostate, kidney, and pancreatic cancers, whereas older cohorts showed elevated risks for stomach, liver, colon, and biliary cancers. Lung cancer trends diverged by sex, decreasing among men but increasing among women. Conclusions: Marked heterogeneity in long-term incidence patterns across cancer types and generations was identified. Rising rates of lifestyle- and obesity-associated cancers in more recent cohorts highlight the need for continued surveillance and targeted prevention strategies. APC-based evaluation provides essential insight into Korea's evolving cancer landscape and supports future public health planning.