AbstractThis study addresses a long‐standing scientific puzzle regarding ionospheric F2 region dynamics. Incoherent scatter radar observations of F2 region plasma drifts showed a strong anticorrelation between temporal variations of field‐aligned upward plasma velocity (Vi‖) and field‐perpendicular poleward plasma drift (Vi ⊥ N) over time scales from a few hours to a day at middle latitudes. The underlying physical processes remain a highly controversial issue, despite a number of speculations and qualitative inspections. Previous studies lacked especially quantitative analysis that could lead to decisive conclusions. In this study, we provide a comprehensive modeling study to explore the physical processes relating Vi‖ with Vi ⊥ N variations using a self‐consistent Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model. It is found that the anticorrelation between Vi‖ and Vi ⊥ N has strong altitudinal and latitudinal dependences. The anticorrelation between the diurnal variations of Vi‖ and Vi ⊥ N is associated with the neutral wind dynamo. Poleward meridional winds result in downward Vi‖ and poleward Vi ⊥ N, and vice versa. The anticorrelation between short‐term temporal disturbances of Vi‖ and Vi ⊥ N is mainly caused by ion drag, in response to high‐latitude convection electric field forcing. This forcing penetrates to lower latitudes and affects poleward plasma drifts Vi ⊥ N, which drags poleward meridional winds and modulates downward Vi‖. As the enhanced convection electric fields subside, the anticorrelation is mainly associated with disturbance meridional wind dynamo. The storm time high‐latitude energy and momentum inputs change global meridional winds which modify zonal electric fields to induce Vi ⊥ N changes. Furthermore, ambipolar diffusion plays a significant role in modulating the relationship between Vi‖ and Vi ⊥ N.