Photo-Fenton degradation of pollutants in wastewater is an ideal choice for large scale practical applications. Herein, two-dimensional (2D) in-plane CuS/Bi2WO6 p-n heterostructures have been successfully constructed by an in situ assembly strategy and characterized using XRD, XPS, SEM/TEM, EDX, UV-Vis-DRS, PL, TR-PL, ESR, and VB-XPS techniques. The XPS and the TEM results confirm the formation of CuS/Bi2WO6 heterostructures. The as-constructed CuS/Bi2WO6 showed excellent absorption in visible region and superior charge carrier separation efficiency due to the formation of a type-II heterojunctions. Under visible light irradiation, 0.1% CuS/Bi2WO6 heterostructure exhibited the best photo-Fenton-like catalytic performance. The degradation efficiency of Rhodamine B (RhB, 20 mg·L−1) can reach nearly 100% within 25 min, the apparent rate constant (kapp/min−1) is approximately 40.06 and 3.87 times higher than that of pure CuS and Bi2WO6, respectively. The degradation efficiency of tetracycline hydrochloride (TC-HCl, 40mg·L−1) can reach 73% in 50 min by employing 0.1% CuS/Bi2WO6 heterostructure as a photo-Fenton-like catalyst. The promoted photo-Fenton catalytic activity of CuS/Bi2WO6 p-n heterostructures is partly ascribed to its low carriers recombination rate. Importantly, CuS in CuS/Bi2WO6 heterostructures is conducive to the formation of heterogeneous photo-Fenton catalytic system, in which Bi2WO6 provides a strong reaction site for CuS to avoid the loss of Cu2+ in Fenton reaction, resulting in its excellent stability and reusability. The possible photo-Fenton-like catalytic degradation mechanism of RhB and TC-HCl was also elucidated on the basis of energy band structure analysis and radical scavenger experiments. The present study provides strong evidence for CuS/Bi2WO6 heterostructures to be used as promising candidates for photo-Fenton treatment of organic pollutants.