<p>The input-output method (IOM) is one of the most popular methods of estimating the ice sheet mass balance (MB), with a significant advantage in presenting the dynamics response of ice to climate change. Assessing the uncertainties of the MB estimation using the IOM is crucial to gaining a clear understanding of the Antarctic ice-sheet mass budget. Here, we introduce a framework for assessing the uncertainties in the MB estimation due to the methodological differences in the IOM, the impact of the parameterization and scale effect on the modeled surface mass balance (SMB, input), and the impact of the uncertainties of ice thickness, ice velocity, and grounding line data on ice discharge (D, output). For the assessment of the D’s uncertainty, we present D at a fine scale. Compared with the goal of determining the Antarctic MB within an uncertainty of 15 Gt yr<sup>−1</sup>, we found that the different strategies employed in the methods cause considerable uncertainties in the annual MB estimation. The uncertainty of the RACMO2.3 SMB caused by its parameterization can reach 20.4 Gt yr<sup>−1</sup>, while that due to the scale effect is up to 216.7 Gt yr<sup>−1</sup>. The observation precisions of the MEaSUREs InSAR-based velocity (1–17 m yr<sup>−1</sup>), the airborne radio-echo sounder thickness (±100 m), and the MEaSUREs InSAR-based grounding line (±100 m) contribute uncertainties of 17.1 Gt yr<sup>−1</sup>, 10.5 ± 2.7 Gt yr<sup>−1</sup> and 8.0~27.8 Gt yr<sup>−1</sup> to the D, respectively. However, the D’s uncertainty due to the remarkable ice thickness data gap, which is represented by the thickness difference between the BEDMAP2 and the BedMachine reaches 101.7 Gt yr<sup>−1</sup>, which indicates its dominant cause of the future D’s uncertainty. In addition, the interannual variability of D caused by the annual changes in the ice velocity and ice thickness are considerable compared with the target uncertainty of 15 Gt yr<sup>−1</sup>, which cannot be ignored in annual MB estimations.</p>