As our world becomes increasingly interconnected, complex global challenges necessitate cross-cultural collaborative efforts. Thus, developing cosmopolitan literacies among students and teachers becomes ever more important. Believing that cosmopolitan literacies are central to being literate in contemporary times, the authors build on their existing project-based inquiry model to include global themes (e.g., poverty, global water and sanitation, climate change) and cross-cultural exchange. This theory-into-practice article explains the Project-Based Inquiry Global process and six design features that enable teachers to facilitate collaborative inquiry projects with their students. As students interact during the process, they begin to practice cosmopolitan literacies by engaging in reading, writing, and inquiry with people and topics from around the world, becoming cross-cultural difference makers.