A block-design experiment was conducted using fMRI to examine the brain regions that activate during the execution of an isometric handgrip exercise performed at light-to-moderate-intensity in the presence of music. Nineteen healthy adults (7 women and 12 men; M age = 24.2, SD = 4.9 years) were exposed to an experimental condition (music [MU]) and a no-music control condition (CO) in a randomized order within a single session. Each condition lasted for 10 min and participants were required to execute 30 exercise trials (i.e., 1 trial = 10 s exercise + 10 s rest). Attention allocation, exertional responses, and affective changes were assessed immediately after each condition. The BOLD response was compared between conditions to identify the combined effects of music and exercise on neural activity. The findings indicate that music reallocated attention toward task-unrelated thoughts (d = 0.52) and upregulated affective arousal (d = 0.72) to a greater degree when compared to a no-music condition. The activity of the left inferior frontal gyrus (lIFG) also increased when participants executed the motor task in the presence of music (F = 24.65), and a significant negative correlation was identified between lIFG activity and perceived exertion for MU (limb discomfort: r = −0.54; overall exertion: r = −0.62). The authors hypothesize that the lIFG activates in response to motor tasks that are executed in the presence of environmental sensory stimuli. Activation of this region might also moderate processing of interoceptive signals – a neurophysiological mechanism responsible for reducing exercise consciousness and ameliorating fatigue-related symptoms.