In this research, the effects of different production parameters and number of tensile fatigue cyclic loads on the breaking strength of core-spun yarns before and after tensile fatigue cyclic loads were studied using Taguchi’s experimental design. A custom-built instrument for evaluating the tensile fatigue of fibrous materials under cyclic loads was used in this study. Based on the Taguchi method 18 samples were manufactured. Polyester and nylon multifilament yarn and three kinds of sheath material, namely, polyester/cotton (80/20), polyester, and viscose fiber were used. Fatigue behavior of core-spun yarns was evaluated after 100, 500 and 1000 cyclic loads. English twist factors (αe) 3.2, 3.5, and 3.8 were applied to core-spun yarns and core pre-tensions of 0, 30, and 60g.were used. Experimental results show a reduction and, in some cases, an increase in breaking strength after cyclic loading. A microtome technique was used to evaluate the cross-section of the yarns. Twist factor was found to be the dominant effect on the fatigue value of core-spun yarns after cyclic loads. The results also show that the ranking of effective parameters on breaking strength vary before and after cyclic loads.