Estimating dissipation timeframes and contaminant mass discharge rates of dense non-aqueous phase liquids (DNAPLs) source zones is of key interest for environmental-management support. Upscaled mathematical modeling of DNAPL dissolution provides a practical approach for assimilating site characterization and downgradient monitoring data to constrain future system behavior. Yet significant uncertainties on predictions of source zone dissipation rates may arise from inadequate or inaccurate conceptual assumptions in parameterization designs. These implications were investigated through upscaled modeling, sensitivity, and uncertainty analyses of high-resolution flow-cell experiments. Sensitivity results emphasized the role of local groundwater velocity and source dimensions in mass transfer scaling by strongly influencing error with respect to DNAPL persistence and dissolution rates. Linear uncertainty analyses, facilitated by PEST ancillary software, demonstrated the worth of monitoring profiles for constraining DNAPL saturations and dispersive mass transfer rates, responsible for source zone longevity. Nonlinear analyses performed with the iterative ensemble smoother PESTPP-iES, facilitated the quantification of unbiased source dissipation uncertainties from DNAPL delineation data. Conversely, monitoring data assimilation without consideration of flow-field heterogeneity and saturation distribution along the flow path biased model predictions. Our analyses provided practical recommendations on upscaled model design to assimilate available site data and support remedial-decision making.