In recent years, there has been growing interest in multimodal literacies used in various teaching and learning contexts, especially in K-12 classrooms. To develop multiple abilities of students, K-12 teachers tend to utilize both print-based and digital texts to facilitate instructional practices in class. However, there are few syntheses of the existing scholarly work to explore how instructional practices of multimodal literacies can effectively support different lingual and cultural backgrounds of students in K-12 education. The current study reviews the empirical research that focused on multimodal literacies in K-12 instructional practices from 2000 to 2020, considering how educators utilized multimodal literacies in different content areas to develop multiple competences of students. Through a systematic literature review method, we analyzed the empirical research focused on teaching and learning effectiveness with multimodal literacies in different K-12 classroom settings. We close with a discussion of the implications of these findings for educators and future directions of this work.