Previous studies have established that the y component of the interplanetary magnetic field (IMF By) plays a role in the north-south asymmetry of the high-latitude plasma convection and wind. The effect of the positive/negative IMF By in the Northern Hemisphere resembles the effect that the negative/positive IMF By would have in the Southern Hemisphere. In this study, we demonstrate that the IMF By effect can also contribute to the hemispheric asymmetry of the thermospheric density. We use high-accuracy air drag measurements from the CHAllenging Minisatellite Payload (CHAMP) satellite and SuperMAG AE index during the period 2001–2006 to examine the response of the high-latitude thermospheric density to geomagnetic activity. Our statistical analysis reveals that the density response at 400 km is greater in the Southern Hemisphere under positive IMF By conditions, and greater in the Northern Hemisphere under negative IMF By conditions. The results suggest that the IMF By effect needs to be taken into account in upper atmospheric modeling for an accurate description of high-latitude densities during periods of enhanced geomagnetic activity.