Ghana education system has failed to effectively address the needs of pupils with learning difficulties (LDs) in regular classrooms. Underachievement, school dropout, streetism, and antisocial behaviors are the consequences. Teachers’ lack of adequate competence in adaptive instruction is one of the fundamental reasons responsible for this anomaly. This study aims to examine teachers’ competence in adapting instructions to teach pupils with LDs in the regular classroom in Ghana. The data were gathered from 387 sampled teachers in a cross-sectional survey using questionnaires and structured observation methods. We analyzed the data using descriptive statistic, chi-square test, correlation, t test, and ANOVA. The results show that (a) teachers have limited to moderate competence in adaptive instruction, (b) adaptive teaching is strongly associated with teachers’ competence in teaching pupils with LDs in the regular classroom, and (c) apart from gender and class size, teachers’ background variables such as school location and teaching experience differ significantly. The study has serious implications for Ghana’s inclusive education policy and teaching practice.