Hypersonic transport fueled with liquid hydrogen (LH2-HST) is currently considered as long-term future technology of civil aviation to fly with speeds greater than Mach 5 at stratospheric altitudes of 25–38 km. In this paper, we present a comprehensive methodology to assess the emission mitigation potential (via NOx and H2O) of future LH2-HST through operational measures, considering realistic constraints such as the sonic boom carpet as well as tolerable g-forces acting on the passengers while flying with hypersonic speeds. Both NOx- and H2O-optimal 4D-trajectories are identified by a brute-force algorithm that varies the initial cruise altitude from 30 to 36 km. As case study, the Mach 8 passenger aircraft STRATOFLY-MR3, which was conceptually developed in the framework of the H2020 STRATOFLY project, is operated on a single route from Brussels (BRU) to Sydney (MYA). The findings are highlighted as relative changes regarding MR3's design flight altitude set at 32 km, respectively, 105 000 ft. As scientific contribution, 3D emission inventories are calculated and made publicly available for a world fleet of MR3 aircraft operated along the BRU-MYA route on both NOx- and H2O-optimal mission profiles in the year 2075.