A solid rocket motor (SRM) with a high aspect ratio that performs normally during ground tests may experience instability during flight. To address this issue, this study employs the pulse triggering method and the numerical approach of two-way fluid–structure interaction to investigate the mechanisms behind the SRM instability resulting from distinctions between on-ground and in-flight conditions. The results indicate that the main distinctions between the on-ground and in-flight conditions for SRMs are the strong constraints during the ground test, as well as aerodynamic forces and aerodynamic heating during flight. The strong constraints in the ground test effectively suppress structural vibrations by limiting displacements. In flight conditions, the aerodynamic heating reduces the strength of the SRM casing and aerodynamic forces provide sustained energy input for structural vibrations during flight. The mechanism for the ground/flight differences that induce SRM instability is that the structural natural frequencies are reduced by aerodynamic heating and the first-order acoustic frequency increased by the propellant regression approach reaches the resonance condition. Therefore, an instability factor Φ is proposed to represent the resonance relationship between the structural natural modes and the acoustic mode of SRMs. Furthermore, the closer the frequency of the aerodynamic forces is to the resonance frequency of the acoustic-structure coupling, the more pronounced the SRM instability.