A comprehensive study of the solar wind interaction with the Martian upper atmosphere is presented. Three global models: the 3‐D Mars multifluid Block Adaptive Tree Solar‐wind Roe Upwind Scheme MHD code (MF‐MHD), the 3‐D Mars Global Ionosphere Thermosphere Model (M‐GITM), and the Mars exosphere Monte Carlo model Adaptive Mesh Particle Simulator (M‐AMPS) were used in this study. These models are one‐way coupled; i.e., the MF‐MHD model uses the 3‐D neutral inputs from M‐GITM and the 3‐D hot oxygen corona distribution from M‐AMPS. By adopting this one‐way coupling approach, the Martian upper atmosphere ion escape rates are investigated in detail with the combined variations of crustal field orientation, solar cycle, and Martian seasonal conditions. The calculated ion escape rates are compared with Mars Express observational data and show reasonable agreement. The variations in solar cycles and seasons can affect the ion loss by a factor of ∼3.3 and ∼1.3, respectively. The crustal magnetic field has a shielding effect to protect Mars from solar wind interaction, and this effect is the strongest for perihelion conditions, with the crustal field facing the Sun. Furthermore, the fraction of cold escaping heavy ionospheric molecular ions [(
and/or
)/Total] are inversely proportional to the fraction of the escaping (ionospheric and corona) atomic ion [O+/Total], whereas
and
ion escape fractions show a positive linear correlation since both ion species are ionospheric ions that follow the same escaping path.