Membrane fouling is a major obstacle for ultrafiltration (UF) in water treatment. Here, a strategy for fouling mitigation, by applying an ultra-low concentration of moderately-hydrophobic chitosan (MHC) and using a mildly elevated backwash temperature was proposed. The effects of MHC type, concentration, and backwash temperature were investigated in continuous-flow tests using PVDF hollow fiber membranes and model raw water. Compared to the process without MHC, or with the addition of chitosan or conventional coagulant polyaluminum chloride, the MHC-based UF system under optimal conditions (MHC: 0.01 mg/L; backwash water temperature: 40 °C) demonstrated its superiority with reduction of ~55% reversible fouling (RR) and ~80% irreversible fouling (IRR), as well as improved effluent quality. A mechanistic study by experimental analyses and theoretical computations revealed that the improved performance of the MHC-based UF process was attributed to the following: (1) MHC inhibited contaminant accumulation on the membrane through a hydrophilization surface-modification effect on the PVDF; (2) increased backwash temperature promoted fouling release (by destabilizing the cake layer structure) and enhanced the surface-modification effect. The additional cost of MHC dosing and backwash water heating was estimated at ~0.126 Chinese Yuan per ton of produced water, and the environmental risk of applying MHC was lower than that of conventional water treatment chemicals. In summary, the MHC-based process has the potential to be a feasible and cost-effective approach for UF fouling control.