BK polyomavirus (BKPyV) causes premature renal failure in 10% to 30% of kidney transplant recipients (KTRs). Current guidelines recommend screening for new-onset BKPyV-DNAemia/nephropathy and reducing immunosuppression to regain BKPyV-specific immune control. Because BKPyV encompasses 4 major genotype (gt)-encoded serotypes (st1,-2,-3,-4), st-specific antibodies may inform the risk and course of BKPyV-DNAemia/nephropathy. Using BKPyV st-virus-like particle (VLP) enzyme-linked immunosorbent assay, we analyzed plasma from 399 blood donors (BDs) and 428 KTRs (134 KTR-cases with BKPyV-DNAemia, 294 KTR-controls). BDs were anti-BKPyV-VLP immunoglobulin G-seropositive in 85% compared to 93% of KTRs at the timepoint at transplantation (T0) (P < .001). Anti-st1 was predominant in both groups followed by anti-st4, anti-st2, and anti-st3. Antibody levels and quadruple sero-reactivity at T0 were higher in KTR-controls than in KTR-cases (P = .026) or in BDs (P < .001). In KTR-cases, anti-st increased posttransplant (P < .0001) and independently of ongoing or cleared BKPyV-DNAemia. However, anti-st levels were significantly higher at T0 in KTR-cases able to clear at timepoint 6-month posttransplant or timepoint 12-month posttransplant. In 34 KTR-cases with deep genome sequencing, BKPyV-gtI was predominant, and anti-st1 and st1-neutralizing antibodies were significantly lower at T0 than in KTR-controls. Thus, BKPyV st-specific antibody levels at transplantation might reflect gt/st-BKPyV-specific immunity clearing or preventing BKPyV-DNAemia in KTR-cases or KTR-controls, respectively. Accordingly, active or passive immunization may be most efficient pretransplant or early posttransplant.