Fatigue is one of the factors affecting the performance of athletes. By understanding the consequences and impact of fatigue on the performance of individuals, certain considerations can be taken into account to prevent it during exercises. Therefore, knowing what an athlete goes through while experiencing central and peripheral fatigue can be the key to success for coaches. Thus, the present study aims to determine the effect of central and peripheral fatigue on throwing accuracy and velocity of handball players. To this purpose, 16 female players of University of Tehran Handball team (with the average age of 23± 4) were selected to participate in the study. Giving their informed consent and filling the Edinburgh Handedness Inventory questionnaire, participants took throwing accuracy and velocity pre-test for 11 times consecutively. Thereafter, they were assigned into two groups randomly: central fatigue group and peripheral fatigue group. Two-hour high-intensity physical exercise was used for the peripheral fatigue group and Stroop task was used for central fatigue group to induce mental fatigue. After the given intervention, post-test was conducted similar to the pre-test. Results of 2×2 compound variance of velocity variable indicated that main effect of test (P = 0. 021) and interaction effect between group and test (P = 0. 01) were significant. However, main effect of group (P = 0. 19) was non-significant. Independent t-test results revealed that there is a significant difference between throwing velocity of the two groups (P = 0. 024) in post-test, and peripheral fatigue group showed lesser velocity rate compared to central fatigue group. Nonetheless, regarding accuracy variable, no significance was found in the main effect of group (P = 0. 24) and interaction effect between test and group (P = 0. 42). Therefore, according to dynamic systems theory, peripheral fatigue has a negative impact on external features of movement, and it is as a result of reduced capacity of effectors; however, central fatigue fails to affect kinetic parameter (velocity).