The purpose of this study was to determine the muscle activation and co-activation of selected muscles during the kettlebell single arm swing exercise. To the best of our knowledge, this is the first study investigating the muscle co-activation of a kettlebell single arm swing exercise. Nine volunteers participated in the present study (age: 22.6 ± 3.8 years; body mass: 80.4 ± 9.2 kg; height: 175.6 ± 7.5 cm). The electrical muscle activity of eight right agonist/antagonist muscles (AD/PD, ESL/RA, ESI/EO, and GM/RF) were recorded using a surface EMG system (Myon m320RX; Myon, Switzerland) and processed using the integrated EMG to calculate a co-activation index (CoI) for the ascending and descending phases. A significant effect of the ascending and descending phases on the muscles’ CoI was observed. Post hoc analyses showed that the co-activation was significantly higher in the descending phase compared to that in the ascending phase of AD/PD CoI (34.25 ± 18.03% and 24.75 ± 13.03%, p < 0.001), ESL/RA CoI (34.97 ± 17.86% and 24.19 ± 10.32%, p < 0.001), ESI/EO CoI (41.14 ± 10.72% and 30.87 ± 11.26%, p < 0.001), and GM/RF CoI (27.49 ± 12.97% and 34.98 ± 14.97%, p < 0.001). In conclusion, the co-activation of the shoulder muscles varies within the kettlebell single arm swing. The highest level of co-activation was observed in the descending phase of AD/PD and GM/RF CoI, and the lowest level of co-activation was observed during the descending phase, ESL/RA and ESI/EO CoI. In addition, the highest level of co-activation was observed in the ascending phase of ESL/RA and ESI/EO CoI, and the lowest level of co-activation was observed during the ascending phase, AD/PD and GM/RF CoI. The co-activation index could be a useful method for the interpretation of the shoulder and core muscles’ co-activity during a kettlebell single arm swing.