Possession of prior knowledge has been shown to critically influence students' learning in major courses. Yet the topic remains unexplored in the realm of general education in higher education. The study aims at investigating whether students lacking relevant high school knowledge background could benefit in the two courses, one inclined to science and one inclined to the humanities, in a general education program at a university in Hong Kong. Interactive learning has been intensively practiced in the program to minimize the unfavorable impact brought up by a lack of prior knowledge among students. Data from an entry-exit survey show that a lack of prior knowledge does not limit students' learning in outcomes related to generic cognitive skills and subject matter content in both courses. An interactive learning approach is suggested to have mediated the problem of the lack of prior knowledge in students' subsequent learning in the two general education courses.