Background: The rapid spread of COVID-19 has placed tremendous strain on the American healthcare system. Few prior studies have evaluated the well-being of or changes to training for American resident physicians during the COVID-19 pandemic. We aim to study predictors of trainee well-being and changes to clinical practice using an anonymous survey of American urology residents. Methods: An anonymous, voluntary, 47-question survey was sent to all ACGME-accredited urology programs in the United States. We executed a cross-sectional analysis evaluating risk factors of perception of anxiety and depression both at work and home and educational outcomes. Multiple linear regressions models were used to estimate beta coefficients and 95% confidence intervals. Results: Among approximately 1,800 urology residents in the USA, 356 (20%) responded. Among these respondents, 24 had missing data leaving a sample size of 332. Important risk factors of mental health outcomes included perception of access to PPE, local COVID-19 severity, and perception of susceptible household members. Risk factors for declination of redeployment included current redeployment, having children, and concerns regarding ability to reach case minimums. Risk factors for concern of achieving operative autonomy included cancellation of elective cases and higher level of training. Conclusions: Several potential actions, which could be taken by urology residency program directors and hospital administration, may optimize urology resident well-being, morale, and education. These include advocating for adequate access to PPE, providing support at both the residency program and institutional levels, instituting telehealth education programs, and fostering a sense of shared responsibility of COVID-19 patients.