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Inquiry is featured prominently in the Next Generation Science Standards (NGSS) as a promising pedagogical approach. Building on current conceptions of inquiry, a mixed-methods research design was used to explore the effects of Project-Based Inquiry (PBI) Global on student science content knowledge, motivation, and perspectives related to inquiry in a cross-school collaboration. The data sources included pre-/post-tests on science content and student motivation (n = 75), transcripts from student focus groups (n = 26), and students’ multimodal learning products (n = 18 teams). The quantitative findings indicated School B students were more motivated by the project than School A students, which mirrored student performance. The student focus group findings generated three themes: constructing empathy, learning for impact, and navigating challenges. The discussion focuses on an integrated view of what students gained and did not gain from the PBI Global experience, including a nuanced explanation of how motivation and content knowledge may be influenced by student experiences and school contextual factors during PBI Global. Implications for instructional practice highlight how relationship building, mutual respect, and consensus making are essential components of constructing cross-school collaborations and the importance of integrating instructional frameworks with teachers and students. Future research will focus on investigating the effects of PBI Global on student learning in cross-school partnerships through experimental-designed studies, and the systemic and structural barriers to scaling cross-school inquiry-based learning.