Background: The recruitment of experienced clinical nurses into vacant faculty positions is a global strategy for preparing, employing, and retaining competent nurse educators. As clinical nurses transition to academia, many struggle with unique challenges that affect their adaptation to the academic setting. Thus, understanding novice nurse educators’ transitional challenges is critical to addressing this threat. Aim: This study aimed to explore the challenges of novice nurse educators’ transition from clinical practice to academia in Ghana. Methods: A descriptive qualitative study design was employed for this study. A purposive sampling technique was used to recruit 12 novice nurse educators from three health training institutions in the Upper East Region of Ghana. A semi-structured interview guide was used to collect data through in-depth individual interviews. The interviews were audio-recorded, transcribed verbatim, and thematically analyzed. Results: Four themes emerged: poor administrative support, poor preparation, increased workload and stress, and role ambiguity. Novice nurse educators lacked formal orientation, formal mentorship, formal education in teaching, and post-graduate education. Novices were also challenged by increased workload and role ambiguity. Conclusion: Supporting novice nurse educators' transition from clinical practice would be better served by college administrators’ creation and implementation of formal orientation and mentorship programs.