Health misinformation on social media can negatively affect knowledge, attitudes, and behaviors, undermining clinical care and public health efforts. Therefore, it is vital to better understand the public's experience with health misinformation on social media. The goal of this analysis was to examine perceptions of the social media information environment and identify associations between health misinformation perceptions and health communication behaviors among US adults. Analyses used data from the 2022 Health Information National Trends Survey (N=6252). Weighted unadjusted proportions described respondents' perceptions of the amount of false or misleading health information on social media ("perceived misinformation amount") and how difficult it is to discern true from false information on social media ("perceived discernment difficulty"). Weighted multivariable logistic regressions examined (1) associations of sociodemographic characteristics and subjective literacy measures with misinformation perceptions and (2) relationships between misinformation perceptions and health communication behaviors (ie, sharing personal or general health information on social media and using social media information in health decisions or in discussions with health care providers). Over one-third of social media users (35.61%) perceived high levels of health misinformation, and approximately two-thirds (66.56%) reported high perceived discernment difficulty. Odds of perceiving high amounts of misinformation were lower among non-Hispanic Black/African American (adjusted odds ratio [aOR] 0.407, 95% CI 0.282-0.587) and Hispanic (aOR 0.610, 95% CI 0.449-0.831) individuals compared to White individuals. Those with lower subjective health literacy were less likely to report high perceived misinformation amount (aOR 0.602, 95% CI 0.374-0.970), whereas those with lower subjective digital literacy were more likely to report high perceived misinformation amount (aOR 1.775, 95% CI 1.400-2.251). Compared to White individuals, Hispanic individuals had lower odds of reporting high discernment difficulty (aOR 0.620, 95% CI 0.462-0.831). Those with lower subjective digital literacy (aOR 1.873, 95% CI 1.478-2.374) or numeracy (aOR 1.465, 95% CI 1.047-2.049) were more likely to report high discernment difficulty. High perceived misinformation amount was associated with lower odds of sharing general health information on social media (aOR 0.742, 95% CI 0.568-0.968), using social media information to make health decisions (aOR 0.273, 95% CI 0.156-0.479), and using social media information in discussions with health care providers (aOR 0.460, 95% CI 0.323-0.655). High perceived discernment difficulty was associated with higher odds of using social media information in health decisions (aOR 1.724, 95% CI 1.208-2.460) and health care provider discussions (aOR 1.389, 95% CI 1.035-1.864). Perceptions of high health misinformation prevalence and discernment difficulty are widespread among social media users, and each has unique associations with sociodemographic characteristics, literacy, and health communication behaviors. These insights can help inform future health communication interventions.