In this work, MoS2/FeS2 nanocomposites were synthesized by a green and simple one-step hydrothermal method to improve the poor Fenton-like activity of MoS2. A series of characterization techniques demonstrated that the MoS2 and FeS2 were chemically and firmly bonded through the Mo-S-Fe bonding. Optimization experiments confirmed that MoS2/FeS2-7-12 h provided the best Fenton-active degradation of sulfamethazine (SMZ), with almost all of the SMZ being degraded within 5 min. Mechanistic studies and Density functional theory results indicated that FeS2 coordinated on the MoS2 surface of MoS2/FeS2-7-12 h can enhance the adsorption and activation for H2O2, with an enhanced Bader charge transfer of 0.44 e- and an improved H2O2 adsorption energy of −0.72 eV compared with MoS2 and FeS2. In addition, The formed Mo-S-Fe bonding during the synthesis process can accelerate the redox cycles of Mo(IV)/Mo(V) and Fe(III)/Fe(II), and thus achieving the efficient generation of •OH and •O2−. Cycling tests showed that MoS2/FeS2-7-12 h could still maintain relatively good degradation activity after five cycles, indicating its excellent recyclability. The satisfactory universality, recyclability and performance enabled MoS2/FeS2-7-12 h to serve as a promising candidate for H2O2 activation.