Objectives: Apolipoprotein A (ApoA) and apolipoprotein B (ApoB) are well-established markers in cardiovascular disease, but their roles in chronic kidney disease (CKD) are not well known. Given their opposing functions in lipid metabolism, this study investigated the associations of ApoA, ApoB, and the ApoB/ApoA ratio with incident CKD to assess their clinical relevance. Methods: This study included 373,043 UK Biobank participants without baseline CKD (median age, 58 years; 47% women). ApoA, ApoB, and the ApoB/ApoA ratio were categorized into quartiles. The primary outcome was incident CKD diagnosed with ICD-10 and OPCS-4 codes. Incident CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m², was also assessed in a sub-cohort with creatinine follow-up data. Results: During a median follow-up of 13.7 years, 14,329 (3.84%) participants developed incident CKD. In multivariable-adjusted Cox proportional hazards models, higher quartiles of ApoA were significantly associated with a lower risk of incident CKD relative to Q1 (adjusted HR [95% CI]: Q2, 0.92 [0.86–0.99]; Q3, 0.85 [0.79–0.91]; Q4, 0.79 [0.74–0.86]; P-for-trend <0.001). In contrast, higher quartiles of the ApoB/ApoA ratios were significantly associated with an increased risk of incident CKD compared with Q1 (adjusted HR [95% CI]: Q2, 1.07 [1.00–1.14]; Q3, 1.12 [1.05–1.21]; Q4, 1.31 [1.22–1.41]; P-for-trend <0.001). Similar results were observed with the eGFR-defined CKD outcome. Mediation analysis revealed that the associations of ApoA and the ApoB/A ratio with incident CKD were mediated by HDL cholesterol and VLDL cholesterol lipid components. Conclusion: Higher ApoA levels were associated with a decreased risk of CKD. In contrast, higher ApoB/ApoA ratios were associated with an increased risk, suggesting that apolipoprotein imbalance may serve as a clinically relevant marker for CKD risk stratification, partly through HDL- and VLDL-related lipid pathways.