Pipeline blockage caused by hydrates and wax in subsea pipelines is a major hazard for flow assurance in the petroleum industry. When hydrates and wax coexist in a flow system, the plugging risk is more severe. The effects of wax on hydrate formation, agglomeration process, flow properties, and plugging mechanisms were studied in a high-pressure flow loop using water-in-oil (w/o) emulsion systems. The flow properties of the system with the presence of wax were entirely different from those of the system without wax under the same experimental conditions. Three types of plugging were observed in the flow loop: rapid plugging, transition plugging, and gradual plugging. The interaction relationships between wax crystals, water droplets, and hydrate particles and the formation of wax hydrate aggregates were proposed based on the particle video measurement (PVM) probe observation and the analysis of the fluid viscosity. The mechanisms of different plugging scenarios were presented, which were highly correlated with the temperature and initial flow rate. The presence of wax would impact on the agglomeration process of hydrate particles leading to a catastrophic decrease in the transportation ability and an extremely high plugging risk after hydrate formation in the pipeline.