Flexible conductive rubber composites (CRCs) were prepared based on carbon black–filled oil-extended styrene–butadiene rubber soft matrix. Using a variety of screw designs, the simultaneous effects of the twin-screw extrusion parameters (i.e., kneading element, dispersing position, and screw speed) on the physicoelectrical properties of the CRCs were investigated statistically. The increased intenseness of the extrusion parameters significantly enhances the piezoresistive sensing via the improved filler dispersion, increased rubber–filler interaction, and weakened filler–filler networks. Nevertheless, the influence of the kneading elements on the properties of the CRCs significantly decreases with an increase in the intenseness of the dispersing position or the screw speed, referred to as a “negative interaction.” An extreme intenseness of the screw design causes the excellent piezoresistive sensing of the CRCs, but with undesirable mechanical strength. Because those properties need to be balanced, many methods of adjusting the CRCs to be more suitable for strain-sensor application, in terms of not only piezoresistive performance but also mechanical strength, were thus established.