Purpose Whilst neural and morphological adaptations following resistance training (RT) have been investigated extensively at a group level, relatively little is known about the contribution of specific physiological mechanisms, or pre-training strength, to the individual changes in strength following training. This study investigated the contribution of multiple underpinning neural [agonist EMG (QEMG(MVT)), antagonist EMG (HEMG(ANTAG))] and morphological variables [total quadriceps volume (QUADS(VOL)), and muscle fascicle pennation angle (QUADS0(p))], as well as pre-training strength, to the individual changes in strength after 12 weeks of knee extensor RT. Methods Twenty-eight healthy young men completed 12 weeks of isometric knee extensor RT (3/week). Isometric maximum voluntary torque (MVT) was assessed pre- and post-RT, as were simultaneous neural drive to the agonist -(QEMG(MVT)) and antagonist (HEMGANTAG). In addition QUADS(VOL) was determined with MRI and QUADS0(p) with B-mode ultrasound. Results Percentage changes (Delta) in MVT were correlated to Delta QEMG(MVT) (r = 0.576, P = 0.001), Delta QUADS(VOL) (r = 0.461, P = 0.014), and pre-training MVT (r = -0.429, P = 0.023), but not Delta HEMGANTAG (r = 0.298, P = 0.123) or Delta QUADS0(p) (r = -0.207, P = 0.291). Multiple regression analysis revealed 59.9% of the total variance in Delta MVT after RT to be explained by Delta QEMG(MVT) (30.6%), Delta QUADS(VOL) (18.7%), and pre-training MVT (10.6%). Conclusions Changes in agonist neural drive, quadriceps muscle volume and pre-training strength combined to explain the majority of the variance in strength changes after knee extensor RT (similar to 60%) and adaptations in agonist neural drive were the most important single predictor during this short-term intervention.