The higher education sector faces considerable competition around the world. Accordingly, universities need to make more efforts to increase their competitive advantages. This study aimed to empirically investigate the effect of organizational innovation (OI), knowledge management (KM), and strategic human resource management (SHRM), with a dependent variable of sustainable competitive advantages (SCAs), at Jordanian Universities. For this aim, a specially designed questionnaire has been distributed to study a convenience sample of 400 academic and administrative staff at Jordanian private and public universities, to obtain the required quantitative data. The study’s hypotheses were verified by Baron and Kenny’s mediation regression approach using the software Statistical Package for the Social Sciences (SPSS). The results of the study demonstrate that there is a significant positive relationship between the following pairs of variables: KM and SCA; SHRM and SCA; SHRM and OI; KM and OI; and OI and SCA, whereas OI was found to have a partial and indirect significant mediation impact on the direct relationship between KM and SHRM and universities (organizations) gaining SCAs. Finally, it was concluded that more attention needs to be paid to the OI aspect in organizations and to integrate it with KM and SHRM in a way that promotes SCAs. In addition, we propose that similar studies should be conducted in industries other than education or the education sector in different countries in a way that obtains generalized and representative results.