Amidst an unprecedented Monkeypox outbreak, we aimed to measure knowledge, attitudes, practices and Monkeypox vaccination intentions among the U.S. adult population. We conducted an online cross-sectional survey, representative of the U.S. adult general public in June 2022. We asked participants whether they would receive a Monkeypox vaccine, if they were recommended to do so. Participants also answered questions on their self-assessed level of Monkeypox knowledge, risk perception, perceived exaggeration of the threat, and self-efficacy around Monkeypox. Furthermore, we asked about their trusted sources of information, COVID-19 vaccination status and administered the 6-item Vaccine Trust Indicator (VTI). Survey weights were created based on age, gender and race. We analyzed predictors of Monkeypox vaccination intentions using logistic regression, adjusted for education, age, race and ethnicity. A total of 856 respondents completed the survey, of which 51% (n = 436) were female and 41% (n = 348) had a college degree or higher. If recommended, 46% of respondents intended to get vaccinated against Monkeypox, 29% would not get vaccinated and 25% did not know. Almost half the respondents (47%) found their own knowledge level about Monkeypox poor or very poor. The most trusted sources of information about the outbreak were healthcare professionals and officials, but also known doctors and researchers with a large online following. Only 24% indicated that the U.S. Centers for Disease Control and Prevention should be in charge of the outbreak response. Being vaccinated against COVID-19 was a strong predictor of intention to receive a Monkeypox if recommended (adjusted Odds Ratio (aOR) 29.2, 95% Confidence Interval (CI) 13.1–65.3). Increased risk perception was positively associated with vaccination intentions (aOR 2.6, 95% CI 1.8–3.6), scoring high on the VTI as well (5.4, 95% CI (3.2–9.1). The low levels of self-assessed knowledge, vaccination intentions and influence of COVID-19 vaccination status point to a lack of clear communication.