The objective of this study was to investigate the influence of fiber morphology and molding parameters on the mechanical and physical properties of fiberboards made from rice straw. The rice straw was thermomechanically treated with a twin-screw extruder. Three parameters were investigated: the amount of water added at molding (0–20%), lignin content (0–25%), and the liquid/solid ratio used for extrudate production (0.33–1.07). A Doehlert experimental design was used to evaluate the effects of these factors on fiberboard properties. A liquid/solid ratio of 0.4 at extrudate production, the addition of 5% water at molding, and a lignin content of 8.9% were found to be optimal for bending properties. The fiberboard produced in these conditions had a density of 1414 kg/m3 (i.e. the densest board). Maximum flexural strength and elastic modulus were 50.3 MPa and 8.6 GPa, respectively. A thickness swelling of 23.6% and 17.6% water absorption were observed. The statistical analysis suggested that a good compromise between density and flexural properties could be obtained with the addition of 0% water, a lignin content of 25% and a liquid/solid ratio of 0.33 at extrudate production. Polynomial models suggested that the fiberboards produced in such conditions would have a maximum flexural strength of 50 MPa, an elastic modulus of 6.0 GPa, a density of 1102 kg/m3, and a thickness swelling of 24%.