Lead (Pb), cadmium (Cd), mercury (Hg), and arsenic (As) are among the top 10 pollutants of global health concern. Studies have shown that exposures to these metals produce severe adverse effects. However, the mechanisms underlying these effects, particularly joint toxicities, are poorly understood in humans. The objective of this investigation was to identify and characterize prevalent combinations of these metals and their species in the U.S. NHANES population to provide background data for future studies of potential metal interactions. Exposure was defined as urine or blood levels ≥ medians of the NHANES 2007-2012 participants ≥6 years (n = 7408). Adjusted-odds ratios (adj-OR) and 95% confidence intervals were determined for covariates (age, gender, and race/ethnicity, cotinine and body mass index). Species-specific analysis was also conducted for As and Hg including iAs (urinary arsenous acid and/or arsenic acid), met-iAs (urinary monomethylarsonic acid and/or dimethylarsinic acid), and oHg (blood methyl-mercury and/or ethyl-mercury). For combinations of As and Hg species, age- and gender-specific prevalence was determined among NHANES 2011-2012 participants (n = 2342). Data showed that approximately 49.3% of the population contained a combination of three or more metals. The most prevalent unique specific combinations were Pb/Cd/Hg/As, Pb/Cd/Hg, and Pb/Cd. Age was consistently associated with these combinations: adj-ORs ranged from 10.9 (Pb/Cd) to 11.2 (Pb/Cd/Hg/As). Race/ethnicity was significant for Pb/Cd/Hg/As. Among women of reproductive age, frequency of oHg/iAs/met-iAS and oHg/met-iAs was 22.9 and 40.3%, respectively. These findings may help prioritize efforts to assess joint toxicities and their impact on public health.