Purpose: The purpose of this study was to examine instructors' pedagogical competencies in teaching 21st century skills in between two streams of study. Design/methodology/approach: The study employed a mixed-methods research design. The investigation involved collecting data from 322 instructors using a questionnaire and ten participants for interviewees at the selected universities in Ethiopia. Findings: The results revealed that there were significant differences in the competence of instructors in favor of instructors of natural science. Natural science instructors were relatively more competent in teaching skills such as critical thinking and problem solving, creativity and innovation, communication and information and communication technology. Research limitations/implications: The findings of this study have important implications for universities to have empirical evidence. It provides information about the competency difference between the two streams of study so that it addresses issues for policy improvement. Practical implications: The findings suggested that urgent interventions needed to be undertaken to improve teachers' 21st century pedagogical competence at the selected universities of Ethiopia. Social implications: The intervention on the competence of teachers in teaching 21st century skills will have an impact on creating employable graduates. This can fit them into contemporary life and careers. Originality/value: The paper makes a comparative analysis of the main teaching competencies among teachers of the natural and social sciences. The perspective is interesting, original, and pertinent to contributing knowledge.