Ice loss from the Greenland Ice Sheet increases global sea level, impacts ocean and sea ice conditions in the Atlantic and Arctic Oceans, and alters regional biological productivity and nutrient cycling. However, predictions of ice sheet mass loss are highly sensitive to poorly constrained parameters, atmospheric and oceanic forcing, and model physics. We report on the sensitivity of 21st-century ice loss projections using the MPAS Albany Land Ice (MALI) model to uncertain model parameters, atmospheric and oceanic forcing, and numerical/configuration choices. We configure MALI, a thermomechanically coupled, three-dimensional, higher-order ice flow model, with a von Mises calving law, and effective pressure-dependent (ie. Budd) sliding law using a 1-10 km unstructured mesh of the Greenland Ice Sheet. We follow the ISMIP6-Greenland protocol, with particular emphasis on experiments using climate forcing from RCP 2.5 and 8.5 greenhouse gas emission scenarios simulated by MIROC5. An initial sensitivity analysis of the von Mises threshold stress varied under the RCP 8.5 emission scenario produces mass loss projections that fall within the ISMIP6 ensemble spread, providing confidence in our baseline MALI configuration. Given our use of active calving and Budd-type sliding, forthcoming work will attempt to calibrate the von Mises threshold stress and the sliding exponent to observed mass loss rates. We also conduct sensitivity tests to various model configurations: thermomechanically coupled vs. constant temperature, three-dimensional vs. depth-integrated solution to the momentum balance, and various numerical treatments of time-stepping and advection. In addition to projecting future ice loss, this effort aims to validate the MALI configuration being used in coupled (ie. ocean, land, atmosphere, sea-ice, and ice-sheet) climate model simulations with the DOE’s Energy Exascale Earth System Model.