The current study investigates the interaction of Gamification, and Instructional Design to enhance the Usability of e-Learning in higher education programs. The study also examines the mediating role of Instructional design. Data were collected from a self-structured questionnaire from the academicians and was analyzed through Structural Equation Modelling (SEM). The results of the study confirmed that gamification is a multi-dimensional construct significantly predicted by elements, game dynamics, motivation, and game mechanics. Further, Instructional design partially mediates the relationship between gamification and usability of e-learning. This research demonstrates that Gamification can enhance the learning environment for e-learning students. This study will also inspire educators and course developers to give due consideration to the instructional design and gamification of an online course. The research findings will motivate educators/instructors/course developers to give equal importance to instructional design and gamification as well as to the content.