Synthesis gas fermentation is a promising route for the valorization of steel mill off-gas and for replacing conventional fossil-based isopropyl alcohol (IPA) production. A recent 120 L pilot-scale study reported 85% gas conversion at 90% product selectivity and claimed a negative global warming potential (GWP) without detailed process design. The current paper reports a first-of-a-kind industrial-scale syngas fermentation process that was designed using extractive distillation with glycerol to produce 46 kton year ⁻¹ of 99.1 wt% IPA. The sustainability of an industrial-scale continuous syngas-to-IPA process has not yet been assessed. This study describes the first integrated cradle-to-gate technoeconomic analysis (TEA) and life cycle assessment (LCA), accounting for all emissions scopes, crediting prevented CO ₂ emissions from steel mill off gas, and including steel mill heat replacement. Parametric assessment identified higher CO volumetric mass transfer rate (VMT _CO) and lower dilution rate (D) as key parameters for enhanced sustainability. For improved process design, economic and environmental tradeoffs were observed for lower glycerol bleed and higher VMT _CO. At best, a −44.4% GWP was achieved for a 6.25% increase in VMT _CO to 8.5 g L ⁻¹ h ⁻¹ (12.2 kgCO ₂-eq kg ⁻¹ _IPA; Netherlands case) and a −23.2% in IPA production costs for a 30% decrease in glycerol bleed of 7 wt% (USD 3.28 per kg _IPA, US case) compared with the base-case process.