This explanatory sequential quasi-experimental study investigated the impact of differentiated instruction on reading comprehension attainment in mixed-ability classrooms. Fifty-four tenth grade students from two classes in two different schools took part in the study. They were randomly distributed into an experimental group (n = 27) and control group n = (27). The experimental group was taught reading comprehension following differentiated instruction strategies of homogeneous grouping, tiered assignment and tiered instruction in the areas of content, process and product. The experimental group was supported with modified reading comprehension texts from Action Pack 10, supplementary materials and leveled short stories. The control group was taught in the one-size-fits-all method using Action Pack 10th text books only. The study is a mixed-method design where quantitative and qualitative methods were used to collect data. The main objective was to investigate the effect of differentiated instruction on secondary stage. The researchers used the pre-test/post-test scores to collect the quantitative data followed by a student semi-structured interview after the experiment. T-test results revealed that differentiated instruction was effective in increasing reading comprehension achievement for the early secondary stage. The experimental group outperformed their counterparts in the control group.