Disparities in online health information accessibility are partially due to varying levels of eHealth literacy and perceived trust. This study examined the relationship between eHealth literacy and perceived trust in online health communication channels and sources among diverse sociodemographic groups. A stratified sample of Black/African Americans (n = 402) and Caucasians (n = 409) completed a Web-based survey that measured eHealth literacy and perceived trustworthiness of online health communication channels and information sources. eHealth literacy positively predicted perceived trust in online health communication channels and sources, but disparities existed by sociodemographic factors. Segmenting audiences according to eHealth literacy level provides a detailed understanding of how perceived trust in discrete online health communication channels and information sources varies among diverse audiences. Black/African Americans with low eHealth literacy had high perceived trust in YouTube and Twitter, whereas Black/African Americans with high eHealth literacy had high perceived trust in online government and religious organizations. Older adults with low eHealth literacy had high perceived trust in Facebook but low perceived trust in online support groups. Researchers and practitioners should consider the sociodemographics and eHealth literacy level of an intended audience when tailoring information through trustworthy online health communication channels and information sources.