Little is known about parental awareness of multisystem inflammatory syndrome in children (MIS-C), a rare but severe sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Via a nationally representative, cross-sectional survey of US parents conducted via Ipsos KnowledgePanel from October to November 2021, we used bivariate and multivariable analyses to describe and identify demographic variables associated with parental knowledge of and attitudes toward MIS-C and to examine associations with perceived coronavirus disease 2019 (COVID-19) severity and susceptibility. Response rate was 64.2% (3230/5034). Thirty-two percent of respondents had heard of MIS-C. After adjustment, higher educational level (compared to high school degree; some college: odds ratio [OR], 2.00 [95% confidence interval {CI}, 1.44-2.77]; bachelor's degree or higher: OR, 3.14 [95% CI, 2.26-4.35]), being a healthcare worker (OR, 1.82 [95% CI, 1.37-2.42]), having a child with a chronic medical condition (OR, 1.62 [95% CI, 1.22-2.14]), and experience with more severe COVID-19 (OR, 1.46 [95% CI, 1.14-1.86]) were associated with MIS-C awareness. Respondents with a child aged 12-17 years were less likely to be aware of MIS-C compared to those without (OR, 0.78 [95% CI, .63-.96]), as were male respondents (OR, 0.56 [95% CI, .46-.69]) and respondents aged 18-34 years (OR, 0.72 [95% CI, .54-.94]) compared to those aged 35-44 years. Awareness of MIS-C was associated with higher perceived COVID-19 severity and susceptibility (regression coefficients, 0.18 [95% CI, .10-.25], P < .001; 0.19 [95% CI, .11-.28], P < .001, respectively). This survey highlights the need to increase parental awareness of MIS-C. Future studies should explore how education regarding MIS-C as a complication of SARS-CoV-2 infection could improve understanding of pediatric disease severity and susceptibility.