Fostering the development of students' critical thinking (CT) is regarded as an essential outcome of higher education. However, despite the large body of research on this topic, there has been little consensus on how educators best support the development of CT. In view of some of the controversies surrounding the teaching of CT skills in higher education, this study examined the effects of embedding CT instruction systematically in domain-specific courses (Immersion vs. Infusion) on the acquisition of domain-specific and domain-general CT skills and course achievement. First-year university students (N = 143) enrolled in an introductory physics course were assigned to one of three instructional conditions: Immersion, Infusion, and control. The Immersion and Infusion conditions followed lessons designed systematically based on the First Principles of Instruction model, whereas the control condition followed a regular instruction. Results showed that participants in the Immersion and Infusion conditions significantly outperformed those in the control condition on domain-specific CT proficiency and course achievement. However, neither the Immersion nor the Infusion condition was helpful in fostering the acquisition of domain-general CT skills. The findings generally demonstrated that embedding CT instruction systematically in domain-specific courses requires greater clarity about what set of CT skills could be targeted in domain-specific instruction, how specific subject-matter instruction could be designed considering CT as an integral part of domain-specific instruction, and how best CT outcomes be assessed. Some considerations for the design of CT-supportive learning environments are discussed.