A systematic review and meta-analysis were conducted to examine the effectiveness of facial anthropomorphism of learning material design in improving learning and other relevant outcomes. We searched Web of Science, PsycInfo, and PsycArticle for studies published before February 2023. Learning outcomes included transfer, retention, and comprehension. Other relevant outcomes included affective-motivational, effort, and experience outcomes. Outcomes that were reported in at least five independent experiments were meta-analyzed; otherwise, a narrative synthesis was performed. Subgroup analysis by participants' age and material type was employed for learning outcomes. A total of 33 independent experiments from 13 research articles were identified and analyzed. For learning outcomes, facial anthropomorphism yielded significant improvements in transfer (standardized mean difference [SMD] 0.28, 95% CI 0.15 to 0.40, p < 0.001), retention (SMD 0.31, 95% CI 0.14 to 0.48, p < 0.001), and comprehension (SMD 0.46, 95% CI 0.27 to 0.64, p < 0.001). Anthropomorphism yielded stronger effect in retention among juvenile students and for static learning materials. Additionally, anthropomorphism design achieved significantly positive effects in positive affect, intrinsic motivation, intrinsic motivation change, perceived difficulty, intrinsic cognitive load, germane cognitive load, perceived learning outcome, aesthetics, and enjoyment. Nineteen outcomes were narratively analyzed and mixed results were found. Facial anthropomorphism design of multimedia learning materials can induce positive emotions in learners and improve their intrinsic motivation that in turn facilitates learners' transfer, retention, and comprehension performance. The study provides valuable insights that can guide educators and multimedia designers in applying facial anthropomorphism with learning materials to facilitate learning outcomes.