Game-based learning refers to establishing learning environments that involve digital or non-digital games to enhance students’ knowledge and skill acquisition. Previous studies indicated that game-based learning is superior to the conventional instructional method, but few compared the differences between different game types. This study examined the effects of game-based learning on Chinese middle school students’ learning of science and their self-efficacy. We implemented an experiment to compare the effects between digital and non-digital game-based learning. Our results showed that students in game-based learning groups performed significantly better in the content knowledge assessment and reported higher self-efficacy than the traditional lecture group. No significant difference was found between the digital and non-digital game groups when considering science learning performance, but students of the digital game group showed significantly higher self-efficacy than those of the non-digital game group. Implications of the findings for future research and practice of game-based learning are discussed.