IMPORTANCE: Documenting Americans' stress responses to an unprecedented pandemic and their degree of adherence to CDC guidelines is essential for mental health interventions and policy-making. OBJECTIVE: To provide the first snapshot of immediate impact of COVID-19 on Americans' stress, coping, and guideline adherence. DESIGN: Data were collected from an online workers' platform for survey research (Amazon's Mechanical Turk) from April 7 to 9, 2020. The current data represents the baseline of a longitudinal study. Best practices for ensuring high-quality data were employed. PARTICIPANTS: Individuals who are 18 years of age or older, living in the USA, and English-speaking were eligible for the study. Of 1086 unique responses, 1015 completed responses are included. SETTING: Population-based. MAIN OUTCOMES: Exposure to and stressfulness of COVID-19 stressors, coping strategies, and adherence to CDC guidelines. RESULTS: The sample was 53.9% women (n = 547), with an average age of 38.9 years (SD = 13.50, range = 18-88), most of whom were White (n = 836, 82.4%), non-Hispanic (n = 929, 91.5%), and straight/heterosexual (n = 895, 88.2%); 40% were currently married (n = 407), and 21.6% (n = 219) were caregivers. About half (50.5%) endorsed having at least "mostly" enough money to meet their needs. Respondents' locations across the USA ranged from 18.5% in the Northeast to 37.8% in the South. The most commonly experienced stressors were reading/hearing about the severity and contagiousness of COVID-19, uncertainty about length of quarantine and social distancing requirements, and changes to social and daily personal care routines. Financial concerns were rated most stressful. Younger age, female gender, and caregiver status increased risk for stressor exposure and greater degree of stressfulness. The most frequently reported strategies to manage stress were distraction, active coping, and seeking emotional social support. CDC guideline adherence was generally high, but several key social distancing and hygiene behaviors showed suboptimal adherence, particularly for men and younger adults. CONCLUSIONS AND RELEVANCE: Americans have high COVID-19 stress exposure and some demographic subgroups appear particularly vulnerable to stress effects. Subgroups less likely to adhere to CDC guidelines may benefit from targeted information campaigns. these findings may guide mental health interventions and inform policy-making regarding implications of specific public health measures.