The determination of the blast loading on building structures is a prerequisite for the analyses of dynamic response and damage mode, as well as the blast-resistant design and the structural reinforcement. In determining the blast loadings on building structures with the upgraded computing hardware and software, the low-cost and high-safety numerical simulation methods have increasingly attracted the attention of researchers. In order to improve the computing efficiency and accuracy, and to balance the capacities of both the hardware and the software, by adopting the simplified calculation method, i.e., using symmetry (1D-2D-3D extension) and remapping method, the optimized sets of mesh sizes for the numerical simulation of blast wave propagating for a long distance in large complex block are proposed. Firstly, aiming at the typical near-ground explosion scenarios, e.g., car bombs and ammunition depots, the sensitivity analyses of single-size mesh based on incident wave of air and ground explosions at the scaled distances of 0.2−5.0 m/kg1/3 and 0.2−39.0 m/kg1/3 are carried out, respectively. Secondly, considering the limitations of the software and hardware, a set of gradient mesh sizes against the scaled distances is recommended. Furthermore, based on the remapping technique and the suggested gradient mesh sizes, the incident overpressure and impulse of ground explosion are numerically calculated, and an improved method for correcting the peak overpressure with the scaled distances larger than 10.0 m/kg1/3 is proposed, which is then verified by UFC 3-340-02. Finally, the computing accuracy and efficiency of the proposed optimized mesh sizes are verified by comparing the simulated and experimental overpressures and impulses (71 gauges) in the field explosion test on a full-scaled building. Besides, the applicability of the proposed gradient mesh size in simple reflection field is verified, which provides a reference for the subsequent proportional amplification application of gradient mesh size and the simulation application of blast loadings in more complex reflection environment.