Previous studies of cat and human locomotion have suggested that the nervous system organizes activities of multiple muscles in five muscle groups (muscle synergies) receiving synergy-specific time-dependent inputs. Two synergies contain flexor muscles and two-joint hamstrings and are active during the swing phase and swing-stance transition; the remaining three synergies consist of extensor muscles and two-joint thigh muscles and are active during the stance phase and stance-swing transition. Given a possible locomotor CPG organization, we hypothesized that split-belt locomotion with faster belt speeds of 0.5, 0.7 and 1.0 m/s and slow belt speed of 0.4 m/s (i) would not change the number of muscle synergies but (ii) would more strongly affect muscle contributions to synergies and synergy activation patterns of the hindlimb moving on the faster belt compared to the contralateral hindlimb on the slow belt. We recorded EMG activity of up to 20 muscles in each hindlimb of 9 adult intact cats during split-belt locomotion and computed muscle synergies using nonnegative matrix factorization. We found that 5 synergies accounted for 95% of variance in EMG data in all locomotor conditions. Speeds of the fast belt between 0.5 and 1.0 m/s had the most prominent effects on ipsilateral synergies, especially those active at phase transitions and involving two-joint muscles. Effects of the fast belt on contralateral synergies were relatively small. We concluded that ipsilateral supraspinal drive and/or motion-dependent sensory input to CPG affect the ipsilateral pattern formation network forming muscle synergies to a greater extent compared to the contralateral network.