This study aimed to identify trends in avoidable mortality (AVM) in 16 provincial and metropolitan regions of South Korea and determine the factors influencing AVM. First, the AVM rate (AVMR) was calculated using the Statistics Korea cause-of-death and population data by age and region from 2013 to 2022. Second, a health determinants model was built, and we identified the factors influencing AVM using generalized estimating equations analysis. Although the AVMR per 100,000 people displayed a steadily decreasing trend from 2013 to 2020, it began to increase in 2021. Meanwhile, Jeonnam, Jeonbuk, Gyeongnam, Gyeongbuk, Chungnam, Chungbuk, and Gangwon Provinces showed a higher AVMR than the national average. The analysis revealed that each 1-unit increase in the older adult population, smoking, perceived stress, or nonlocal medical utilization was associated with an increase in the AVMR. Conversely, 1-unit increases in the male-to-female ratio, marriage rate, positive self-rated health, local medical utilization, doctor population, influenza vaccination rate, cancer screening rate, or financial independence were associated with decrease in the AVMR. This study established that the AVMR, which had been continuously decreasing across the 16 regions, shifted to an increasing trend in 2021. We also identified several factors influencing AVM. Further studies are needed to confirm the reasons for this shift in the AVMR and explore the factors that influence AVM across Korea's 16 provincial and metropolitan regions.