Background e-learning was underutilized in the past especially in developing countries. However, the current crisis of the COVID-19 pandemic forced the entire world to rely on it for education. Objectives To estimate the university medical staff perceptions, evaluate their experiences, recognize their barriers, challenges of e-learning during the COVID-19 pandemic, and investigate factors influencing the acceptance and use of e-learning as a tool teaching within higher education. Methods Data was collected using an electronic questionnaire with a validated Technology Acceptance Model (TAM) for exploring factors that affect the acceptance and use of e-learning as a teaching tool among medical staff members, Zagazig University, Egypt Results The majority (88%) of the staff members agreed that the technological skills of giving the online courses increase the educational value of the experience of the college staff. The rate of participant agreement on perceived usefulness, perceived ease of use, and acceptance of e-learning was (77.1%, 76.5%, and 80.9% respectively). The highest barriers to elearning were insufficient/ unstable internet connectivity (40%), inadequate computer labs (36%), lack of computers/ laptops (32%), and technical problems (32%). Younger age, teaching experience less than 10 years, and being a male are the most important indicators affecting e-learning acceptance. Conclusion This study highlights the challenges and factors influencing the acceptance, and use of elearning as a tool for teaching within higher education. Thus, it will help to develop a strategic plan for the successful implementation of e-learning and view technology as a positive step towards evolution and change