The global prevalence and incidence of chronic kidney disease (CKD) continue to increase. Whether hyperuricemia is an independent risk factor for renal progression and whether there are sex differences in the relationships between serum uric acid (UA) and a decline in renal function are unclear. Therefore, in this longitudinal study, we aimed to explore these relationships in a large cohort of around 27,000 Taiwanese participants in the Taiwan Biobank (TWB), and also to identify serum UA cutoff levels in men and women to predict new-onset CKD. A total of 26,942 participants with a median 4 years of complete follow-up data were enrolled from the TWB. We excluded those with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) at baseline (n = 297), and the remaining 26,645 participants (males: 9356; females: 17,289) were analyzed. The participants who developed CKD during follow-up were defined as having incident new-onset CKD, and those with a serum UA level >7 mg/dL in males and >6 mg/dL in females were classified as having hyperuricemia. After multivariable analysis, hyperuricemia (odds ratio [OR], 2.541; 95% confidence interval [CI], 1.970−3.276; p < 0.001) was significantly associated with new-onset CKD. Furthermore, in the male participants (n = 9356), hyperuricemia (OR, 1.989; 95% CI, 1.440−2.747; p < 0.001), and quartile 4 of UA (vs. quartile 1; OR, 2.279; 95% CI, 1.464−3.547; p < 0.001) were significantly associated with new-onset CKD, while in the female participants (n = 17,289), hyperuricemia (OR, 3.813; 95% CI, 2.500−5.815; p < 0.001), quartile 3 of UA (vs. quartile 1; OR, 3.741; 95% CI, 1.250−11.915; p = 0.018), and quartile 4 of UA (vs. quartile 1; OR, 12.114; 95% CI, 14.278−34.305; p < 0.001) were significantly associated with new-onset CKD. There were significant interactions between hyperuricemia and sex (p = 0.024), and quartiles of serum UA and sex (p = 0.010) on new-onset CKD. Hyperuricemia was associated with new-onset CKD in the enrolled participants, and the interactions between hyperuricemia and sex were statistically significant. Hyperuricemia was more strongly associated with new-onset CKD in the women than in the men.