The use of health information technology significantly enhances patient outcomes. As a result, policymakers from developing countries have placed strong emphasis on formulating eHealth policies and initiatives. However, there have not been many successful deployments to show for. The role of individual factors in the successful implementation of these technologies is indispensable. Therefore, this study assesses healthcare professionals’ knowledge, attitudes, and practice of health information technology. An institution-based cross-sectional study was conducted at the University of Gondar Comprehensive Specialized Hospital from November 15 to December 29, 2020. A structured, self-administered questionnaire was used to collect data. Student’s t -test was used to learn if there were any significant differences in practice habits between participants with and without previous information technology-related training. In addition, first-order partial correlation was conducted to identify the relationship of knowledge and attitude with practice. A total of 347 health professionals responded to the questionnaire, yielding an 87.2% response rate. Most health professionals are not aware of how to use health information technologies. Notably, practice levels were low and needed prompt action from responsible authorities. Previous training did not work very well to improve the practice levels of health professionals. However, the positive attitude of these professionals encourages policymakers and implementers to engage closely.