Knowledge on neural processing during complex non-stationary motion sequences of sport-specific movements still remains elusive. Hence, we aimed at investigating hemodynamic response alterations during a basketball slalom dribbling task (BSDT) using multi-distance functional near-infrared spectroscopy (fNIRS) in 23 participants (12 females). Additionally, we quantified how the brain adapts its processing as a function of altered hand use (dominant right hand (DH) vs. non-dominant left hand (NDH) vs. alternating hands (AH)) and pace of execution (slow vs. fast) in BSDT. We found that BSDT activated bilateral premotor cortex (PMC), supplementary motor cortex (SMA), primary motor cortex (M1) as well as inferior parietal cortex and somatosensory association cortex. Slow dominant hand dribbling (DHslow) evoked lower contralateral hemodynamic responses in sensorimotor regions compared to fast dribbling (DHfast). Furthermore, during DHslow dribbling, we found lower hemodynamic responses in ipsilateral M1 as compared to dribbling with alternating hands (AHslow). Hence, altered task complexity during BSDT induced differential hemodynamic response patterns. Furthermore, a correlation analysis revealed that lower levels of perceived task complexity are associated with lower hemodynamic responses in ipsilateral PMC-SMA, which is an indicator for neuronal efficiency in participants with better basketball dribbling skills. The present study extends previous findings by showing that varying levels of task complexity are reflected by specific hemodynamic response alterations even during sports-relevant motor behavior. Taken together, we suggest that quantifying brain activation during complex movements is a prerequisite for assessing brain-behavior relations and optimizing motor performance.