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A main goal of human space exploration is to develop humanity into a multi-planet species where civilization extends beyond planet Earth. Establishing a self-sustaining human presence on Mars is key to achieving this goal. In situ resource utilization (ISRU) on Mars is a critical component to enabling humans on Mars to both establish long-term outposts and become self-reliant. This article focuses on a mission architecture using the SpaceX Starship as cargo and crew vehicles for the journey to Mars. The first Starships flown to Mars will be uncrewed and will provide unprecedented opportunities to deliver ∼100 metric tons of cargo to the martian surface per mission and conduct robotic precursor work to enable a sustained and self-reliant human presence on Mars. We propose that the highest priority activities for early uncrewed Starships include pre-placement of supplies, developing infrastructure, testing of key technologies, and conducting resource prospecting to map and characterize water ice for future ISRU purposes., Competing Interests: No competing financial interests exist., (© Jennifer L. Heldmann, et al. 2022; Published by Mary Ann Liebert, Inc.)