OBJECTIVE The rapid emergence of the coronavirus disease 2019 (COVID-19) pandemic in the United States has dramatically altered daily life and taken a toll on Americans' physical, mental, social, and financial well-being. Based on previous widespread disasters, future high prevalence of short- and long-term adverse mental health consequences are anticipated. Studies of COVID-19 outside the United States indicated moderately high levels of distress, but we have little information regarding Americans' distress nor the factors associated with relative distress or adjustment during this unprecedented time. This study represents the first national view of Americans' distress during the massive disruption of COVID-19 and identifies levels of stress exposure, protective psychosocial resources, and coping strategies. METHODS Data were collected April 7-9, 2020 from an online platform, using best practices for ensuring high-quality data; 1,015 completed respondents are included ([53.9%] women; average age = 38.9 years; mostly White [82.4%] and non-Hispanic [91.5%]). Respondents' locations ranged across the United States, from 18.5% in the Northeast to 37.8% in the South. RESULTS Fairly high levels of stress exposure and peritraumatic and general distress (depression, anxiety, and stress) were reported. Emotion regulation skills along with active and distraction coping emerged as the strongest predictors of lower distress levels. CONCLUSIONS These results identify potential targets for online mental health interventions-focusing on engaging in adaptive emotion regulation and coping (e.g., through telehealth mental health first aid)-during the pandemic to offset the likely rise in distress over the months ahead. (PsycInfo Database Record (c) 2021 APA, all rights reserved).