Background: Handgrip strength (HGS) is a good predictor of adverse health outcomes in later life. This prospective study aimed to investigate whether HGS trajectory patterns were associated with all-cause mortality among older adults in Korea. Methods: This study used the database of the 2006–2016 Korean Longitudinal Study of Aging. Study participants included 3,069 adults aged ≥65 years without a previous history of cancer. The trajectory model was developed to identify different homogeneous trajectory patterns of HGS according to study period. Cox proportional hazards models were then applied to investigate the association between HGS and all-cause mortality. Results: The survival probability according to HGS during the follow-up period decreased as base HGS weakened. We identified four distinct trajectory groups of HGS among men and three among women. The risk of mortality increased as the HGS of both males and females decreased. Compared with the highest HGS group, the adjusted hazard ratios for all-cause mortality of the lowest, lower-mid, and upper-mid HGS groups among males were 3.46 (95% confidence interval [CI], 2.17–6.69), 2.26 (95% CI, 1.47–3.48), and 1.58 (95% CI, 1.07–2.32). Those of the low and mid HGS groups among females were 2.69 (95% CI, 1.39–5.21) and 1.97 (95% CI, 1.05–3.69). Conclusion The faster HGS declined over time, the greater the all-cause mortality risk increased compared with the slowly decreasing or maintained HGS groups among men and women. HGS measurement among older adults will be helpful in assessing their health statuses and pre-assessing disease-associated morbidity.