Anterior cruciate ligament (ACL) injury risk reduction strategies primarily focus on biomechanical factors related to frontal plane knee motion and loading. Although central nervous system processing has emerged as a contributor to injury risk, brain activity associated with the resultant ACL injury-risk biomechanics is limited. Thus, the purposes of this preliminary study were to determine the relationship between bilateral motor control brain activity and injury risk biomechanics and isolate differences in brain activity for those who demonstrate high versus low ACL injury risk. Thirty-one high school female athletes completed a novel, multi-joint leg press during brain functional magnetic resonance imaging (fMRI) to characterize bilateral motor control brain activity. Athletes also completed an established biomechanical assessment of ACL injury risk biomechanics within a 3D motion analysis laboratory. Knee abduction moments during landing were modelled as a covariate of interest within the fMRI analyses to identify directional relationships with brain activity and an injury-risk group classification analysis, based on established knee abduction moment cut-points. Greater landing knee abduction moments were associated with greater lingual gyrus, intracalcarine cortex, posterior cingulate cortex and precuneus activity when performing the bilateral leg press (all z > 3.1, p < .05; multiple comparison corrected). In the follow-up injury-risk classification analysis, those classified as high ACL injury-risk had greater activity in the lingual gyrus, parietal cortex and bilateral primary and secondary motor cortices relative to those classified as low ACL injury-risk (all z > 3.1, p < .05; multiple comparison corrected). In young female athletes, elevated brain activity for bilateral leg motor control in regions that integrate sensory, spatial, and attentional information were related to ACL injury-risk landing biomechanics. These data implicate crossmodal visual and proprioceptive integration brain activity and knee spatial awareness as potential neurotherapeutic targets to optimize ACL injury-risk reduction strategies.