Many ICUs worldwide are striving to integrate early mobilization as part of critical care rehabilitation. However, ICU nurses, who are essential contributors to the early mobilization of critically ill patients, still lack comprehensive surveys assessing their knowledge, beliefs, and practices regarding the early mobilization of mechanically ventilated patients. To analyse the knowledge, attitudes, and practices of intensive care unit (ICU) nurses regarding the early mobilization of mechanically ventilated patients and to explore the effects of these practices. A multicentre cross-sectional study. ICU nurses in five tertiary hospitals in Zhejiang Province, China, were selected by convenience sampling and invited to complete an online questionnaire between 1 June 2021 and 15 June 2021. Sociodemographic data and the knowledge, attitudes, and practices of ICU nurses regarding early mobilization. A total of 296 valid questionnaires were collected, for a response rate of approximately 77.5%. The average scores for knowledge, attitudes, and practices of ICU nurses regarding the early mobilization of mechanically ventilated patients were 42.7 ± 7.4, 34.3 ± 6.5, and 47.1 ± 6.5, respectively, which were good scores. Quantile regressions showed that at the 25% and 50% quartiles, increases in knowledge and attitude scores resulted in increases in practice scores (p < .001); however, at the 75% quartile, increases in knowledge scores did not result in practice score increases (t = 0.000, p = .999); moreover, there was still a 0.5-point increase in practice scores per 1-point increase in attitude scores (t = 0.500, p < .001). The knowledge, attitudes, and self-reported practices of ICU nurses were good, although there is room for improvement. Considering that the influence of attitudes on practice improvement is more important than knowledge, ICU managers should promote knowledge transformation, strengthen attitudes, and adopt comprehensive measures to promote the early mobilization of mechanically ventilated patients in the ICU. To optimize the early mobilization of mechanically ventilated patients in the ICU, introducing multipronged support strategies based on the knowledge and attitudes of ICU nurses is recommended to promote the implementation of such practices.