The effect of different processing routes on structure and properties of high-density polyethylene (HDPE)-clay nanocomposites was assessed. Different compatibilizer/clay ratios (α) were also studied to determine if interactions exist between processing route and polymer-clay compatibility. HDPE/HDPE-g-MA/clay with α values of 1 to 4 were melt compounded (twin screw extrusion), and then processed via three routes: compression moulding, compression moulding followed by biaxial stretching or blown film extrusion. The structure was examined using X-ray diffraction (XRD) and transmission electron microscopy (TEM). Tensile and oxygen barrier properties were determined. It was found that biaxial extensional forming produced the best enhancement in properties. An interaction between processing route and polymer-clay compatibility is evident. Halpin-Tsai (H-T) model was employed to predict relative modulus values. It showed good agreement with the experimental data. For biaxial extension at α = 4.0, the experimental relative modulus is greater than the predicted value. This may indicate the existence of a "nano" effect at the polymer-clay interface.