To understand parental stress resulting from parenting young children, the current literature has primarily focused on families of children with clinical conditions, but has placed far less attention on the general population. The aim of this study was to examine parenting stress related to children’s clinical conditions and behavioral problems in a nationally representative sample of US children aged 3 to 5 years. The study sample included 8454 children aged 3 to 5 years and their parents who participated in the 2018–2019 US National Survey of Child Health (NSCH). Using online/paper NSCH questionnaires, parents reported their children’s special health care needs (SHCN), clinically diagnosed mental, emotional, developmental, and behavioral (MEDB) problems (e.g., anxiety problem, developmental delay), and externalizing behaviors. Parents also reported the frequency of feeling aggravated from parenting the participating child as an indicator of elevated parenting stress. In the sample, the prevalence of elevated parenting stress was 5.1% overall (95% CI = 4.2, 6.0); however, it was significantly higher among parents of children with SHCN (20.8%; 95% CI = 16.7, 24.9), with MEDB problems (24.8%; 95% CI = 19.9, 29.8), and with externalizing behavior problems (14.7%; 95% CI = 11.8, 17.6). A multivariable logistic regression model showed that elevated parenting stress was associated with the child’s SHCN (adjusted odds ratio [AOR] = 2.3; 1.3, 3.9), MEDB problems (AOR = 4.8; 95% CI = 2.5, 9.1), and externalizing behavior problems (AOR = 5.4; 95% CI = 3.1, 9.4). Even in children without SHCN or MEDB problems, externalizing behavior problems were associated with elevated parenting stress (AOR = 6.4; 95% CI = 3.3, 12.7). The findings call for greater attention to subclinical or yet to be diagnosed externalizing behavior problems among the general preschool-aged child population and their underestimated impact on parenting stress.