The use of XR, which encompasses Virtual Reality (VR), Augmented Reality (AR), and Mixed Reality (MR) has evolved rapidly in higher education (HE), driven by advancements in technology and the increasing recognition of its potential to enhance learning experiences. This systematic review provides unique findings with an up-to-date examination of the use of XR in HE from 2020-2024. Using PRISMA principles and protocol, 295 articles were identified for full examination. Using a priori, and grounded coding, the data from the 295 articles were extracted, analyzed, and coded to determine the trends in HE research regarding the use of XR. A priori coding revealed that research was conducted on six continents and in 48 countries, with the US leading in the number of publications. A prior coding also showed that VR was the most frequently used type of XR in the research studies (58%), that the research took place most often in undergraduate settings (81%), and that science was the academic discipline with the most studies (21%). Grounded coding identified three domains regarding the purpose of using XR: knowledge acquisition (51%), psychomotor learning (35%), and affective learning (14%). The grounded coding also revealed that XR was being used in four ways to facilitate learning: (1) Simulation, (2) Visualization, (3) Problem-solving, and (4) Gaming. Lastly, four challenges were identified: (1) Impact on students, (2) Inauthentic environments, (3) Time and money, and (4) Usability and technical issues. This systematic review revealed gaps in the literature to be used as a springboard for future researchers studying the use of XR in HE.