Trace element homeostasis increasingly emerges as a modifiable determinant of chronic airway disease, yet population-level multi-metal data in asthma remain limited. This study aimed to characterize whole-blood concentrations of five clinically relevant metals lead, cadmium, total mercury, selenium, and manganese in adults with and without current physician-diagnosed asthma and to determine which metals independently predict asthma status after adjustment for key sociodemographic and lifestyle confounders. A cross-sectional analysis was conducted using data of adults (292 with current asthma, 225 controls) enrolled in a nationally representative health survey (2017–2020). Blood metals were quantified by inductively coupled plasma–mass spectrometry (ICP-MS). Group differences were examined with the Mann–Whitney U test, with effect sizes expressed as rank-biserial correlation coefficients. Multivariable binary logistic regression with receiver-operating characteristic (ROC) curve validation identified independent predictors. Blood selenium was the sole metal to differ significantly between groups: asthmatic participants exhibited lower concentrations than controls (median 174.5 vs. 178.9 μg/L; p = 0.021, effect size r = 0.10). Although the selenium effect was attenuated after full covariate adjustment (OR = 0.995; 95% CI 0.978–1.013; p = 0.605), the observed direction of association was similar to that reported in previous studies evaluating selenium and asthma. A borderline protective signal for total mercury, likely a surrogate marker of anti-inflammatory omega-3 fatty acid intake from fish, was also detected (OR = 0.524; p = 0.067). Lead, cadmium, and manganese did not differ between groups. The multimetal logistic model achieved modest discrimination (AUC = 0.58; 95% CI = 0.53–0.63). These findings highlight the complexity of selenium–asthma associations and the potential influence of dietary, socioeconomic, and sampling-related confounding. Survey-weighted analyses confirmed that the apparent association was not statistically significant after accounting for the NHANES complex sampling design (weighted p = 0.401).