Background: Assessing awareness and knowledge of the Physical Activity Guidelines for Americans, 2nd edition (Guidelines), released in 2018, is important for monitoring factors that contribute to increasing physical activity. Methods: We estimated prevalence of awareness and knowledge of the adult aerobic guideline (≥150 min/wk of moderate-intensity equivalent aerobic physical activity preferably spread out over a week) among adults (n = 3471) and of the youth aerobic guideline (≥60 min/d of mostly moderate- to vigorous-intensity aerobic physical activity) among a subset of parents (n = 744) from a nationwide sample of US adults in the 2019 FallStyles survey. We estimated odds ratios using logistic regression, adjusting for demographic and other characteristics. Results: Approximately 1 in 10 US adults and parents reported being aware of the Guidelines. Only 3% of adults knew the correct adult aerobic guideline. The most common responses were “don’t know/not sure” (44%) and “30 minutes a day, 5 or more days a week” (28%). Among parents, 15% knew the youth aerobic guideline. Awareness and knowledge tended to be lower with lower education and income. Conclusions: Limited awareness and knowledge of the Guidelines suggest communication about the Guidelines could be strengthened, especially among adults with low income or education.