The emphasis on adapting learner-centric education and inclusive pedagogies to promote learning effectiveness is part of the paradigm shift in teaching. By maximizing variability, differentiated education methodologies ensure individualized instruction and equal academic success for all students. Based on this justification, this study sought to investigate Ghanaian pre-tertiary teachers' adaption of differentiated instruction strategies during the teaching and learning processes. Pre-tertiary teachers within the Kwahu Ridge of the Eastern Region of Ghana were sampled to respond to the close-ended questionnaire. A multi-pronged approach was employed in the data analysis. Respondents possessed knowledge of the differentiated instruction strategies, however, there were some disparities between first and second-cycle teachers. Significant factors influenced the range of diversity in the classroom and knowledge and experience, with the latter showing an unexpected negative influence, possibly due to experienced teachers' preference for traditional methods of teaching. Notwithstanding, a perfect alignment of instructional techniques, activities and assessment practices to accommodate the heterogeneity of students stimulate active participation, interest and readiness to learn. It is recommended that educational stakeholders should recognize the dynamic nature of the learning environment and better provide pre-tertiary teachers with the tools and support needed to employ differentiated instruction techniques successfully to ensure inclusive, individualized and intensive instruction in the classroom.