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Lignin, isolated from switchgrass (Panicum virgatum) and tulip poplar (Liriodendron tulipifera) using organosolv fractionation is currently being explored for its potential use in the production of value-added chemicals and bio-based polymers. Taguchi Robust Product Design (TRPD) was applied to maximize lignin yield from the fractionation process. The following four controllable design factors were used in the TRPD: process temperature (120 °C, 140 °C and 160 °C), fractionation time (56 and 90 min), sulfuric acid concentration (0.025 M, 0.05 M and 0.1 M), and feedstock type (switchgrass/tulip poplar chip ratios of 10/90, 50/50 and 90/10). Process noise was induced in the experiment by using either the mass- or volume-based feedstock charges of switchgrass and tulip poplar chips. A maximum mean lignin yield of 78.63 wt% and signal-to-noise ratio of 37.90 was found at a 90 min runtime, a process temperature of 160 °C, a sulfuric acid concentration of 0.1 M, and a feedstock composition of 10% switchgrass and 90% tulip poplar. Process temperature was the most significant factor that influenced lignin yield. This study may provide a pathway for industrialists and researchers interested in maximizing lignin yield in the organosolv fractionation process.