Major structural features, some cutting the entire lithosphere, are important controls on location and orientation of the time-progressive track of the Yellowstone melting anomaly along the Eastern Snake River Plain (ESRP), inconsistent with the deep-mantle plume theory of origin of this “hotspot”. Numerous NE-trending tectonic features either straddle or align with the ESRP: 1) the pre-Tertiary Humboldt lineament at its SW end; 2) an Early Proterozoic suture between the Archean Wyoming and Hearne Provinces, partly expressed by the Madison and other mylonite zones in the Beartooth Mountains; 3) the Proterozoic Great Falls tectonic zone straddling the north flank of the ESRP; 4) a Late Cretaceous transverse sediment dispersal system (structural recess) in the Sevier orogenic belt; and 5) a change in the orientation and expression of Laramide foreland contractional structures. The spatial coincidence of these features with the Yellowstone track must be explained as mere coincidence if the “hotspot” is driven by a deep-mantle plume. The track also parallels other NE-trending anomalies, including magnetic anomalies beneath the Great Plains of eastern Montana, and the Cheyenne Belt, Saint George trend, Colorado Mineral Belt, and Jemez trend to the south. Collectively, these features define a first-order NE-trending lithospheric tectonic grain. We present a model for the Yellowstone melting anomaly that involves exploitation of preexisting tectonic features to accommodate oblique extensional strain across the Intermountain West since the mid-Miocene. In this model, lithospheric tectonic processes, including subduction, basin-range extension, and northward migration of the Mendocino triple junction interact with sublithospheric upper mantle to produce the NW-propagating Newberry and NE-propagating Yellowstone melting anomalies. Exploitation of preexisting structural weaknesses may explain why the Yellowstone track is magmatically more productive than the Newberry track.