Mission HydroSci (MHS) is a 3D game-based learning environment and curriculum that supports middle school student learning of water systems science and scientific argumentation. MHS is a rigorous, coherent and engaging 6 to 8-day curriculum with all learning activities and social interactions taking place in the virtual world and with teachers observing and supporting students through an online support system enhanced by analytics. MHS was evaluated in comparison to a high- quality alternative intervention developed by the Biological Sciences Curriculum Study (BSCS) using a stratified randomized block experimental design where 'classroom' was the unit of random assignment, stratified by teacher. The comparison curriculum is called Earth's Water Systems (EWS) and is provided online using the Canvas learning management platform. Three measurable outcomes: (1) content knowledge, (2) competency in scientific argumentation, and (3) affect for science and technology were used in the pre- post-comparison of MHS with EWS. The findings of this randomized experiment showed that MHS achieved roughly equivalent water systems learning outcomes and significantly higher development of argumentation competencies when compared to the EWS curriculum. The impacts of both MHS and the EWS curriculum on affect for science and technology were equivalent and slightly negative. A secondary exploratory quasi-experimental design (QED) analysis was conducted that found significant positive effects for MHS in comparison to EWS on water systems understandings and stronger detected effects for students' argumentation.