The role that the motion of microplates has played in the development of the Eastern California Shear Zone in western North America is unclear. It was previously proposed that shear related to Baja California motion has propagated from the Gulf of California northward into Nevada. However, there is evidence that the formation of the Eastern California Shear Zone predates the inception of Baja California motion. Thus, either Baja California began to move northwestward prior to 6Ma, or the Eastern California Shear Zone formed by shear strain resulting from different microplate motion than Baja California. The role of Sierra Nevada motion on the development of an adjacent shear zone remains untested. We present a numerical modeling study that examines the deformational response of western North America to Baja California and/or Sierra Nevada microplate motion. In particular we study if, and under what condition of microplate motion, shear strain can localize in the northern and southern part of the Eastern California Shear Zone (separated by the Garlock fault). We find that given the pre-existing weakness from Miocene Basin and Range extension (a lithospheric strength contrast or normal faults) shear strain from either the Baja California or Sierra Nevada microplates can lead to the formation of the Eastern California Shear Zone. Furthermore, the presence of a pre-existing weakness explains the earlier initiation of strike-slip faulting north of the Garlock fault. Our models suggest that today, Baja California microplate motion is the major player for present-day deformation rates along the Eastern California Shear Zone and was in the past 6Myrs also a major driver of strain localization in southern Eastern California Shear Zone within the Mojave block.