Ethylbenzene and styrene are air toxicants with widespread nonoccupational exposure sources, including tobacco smoke and diet. Ethylbenzene and styrene (EB/S) exposure was quantified from their common metabolites measured in spot urine samples obtained from participants (≥6 years old) in the 2005-2006 and 2011-2012 cycles of the National Health and Nutrition Examination Survey (NHANES; N = 4690). EB/S metabolites mandelic acid (MA) and phenylglyoxylic acid (PGA) were measured using ultra-high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). MA and PGA were detected in 98.9% and 90.6% of tested urine specimens, respectively. Exclusive smokers had 2-fold and 1.6-fold higher median urinary MA and PGA, respectively, compared with non-users. Sampleweighted regression analysis among exclusive smokers showed that smoking 0.5 pack cigarettes per day significantly increased MA (+97.9 μg/L) and PGA (+69.3 μg/L), controlling for potential confounders. In comparison, exposure from the median daily dietary intake of grain products increased MA by 1.95 μg/L and was not associated with statistically significant changes in urinary PGA levels. Conversely, consuming vegetables and fruit was associated with decreased MA and PGA. These results confirm tobacco smoke as a major source of ethylbenzene and styrene exposure for the general U.S. population.