It is important to prevent the increase in the prevalence of diabetes mellitus (DM) worldwide by efficiently managing its controllable risk factors. This study aimed to identify factors associated with the 4-year estimated incidence of type 2 DM (T2DM) by sex and provide basic data for a sex-specific strategic approach to lifestyle modification. We performed a secondary data analysis using raw data from the seventh Korea National Health and Nutrition Examination Survey (KNHANES, 2016–2018). The KNHANES is a descriptive correlational survey designed to examine sex differences in the factors associated with the 4-year estimated incidence of T2DM. This study included 9,614 Korean adults (4,134 men and 5,480 women) aged 40–69 years without a diagnosis of T2DM. For the statistical analysis, a complex sample analysis was performed for sex comparison using the χ2-test or one-way analysis of variance; a multiple regression analysis was performed to analyze the sex-specific influencing variables of 4-year estimated T2DM incidence. The waist-to-height ratio, an indicator of central obesity in adults, showed the strongest association with the 4-year estimated incidence of T2DM in both groups (male: β = 0.33,
p
≤
0.001
; female: β = 0.38,
p
≤
0.001
). The influencing variables were the monthly drinking rate (β = 0.07,
p
≤
0.001
) and sleep time (β = −0.03,
p
<
0.05
) in men and the sedentary time in women (β = 0.03,
p
<
0.05
). The overall explanatory power of these variables was 11.3% for men and 14.3% for women. Thus, significant sex differences were found in the 4-year estimated incidence of T2DM. Therefore, intervention programs need to be sex-specific to enhance the efficacy of the interventions in reducing the incidence of T2DM, and such intervention programs should be administered with a strategic approach differentiated by sex.