Itaconic acid (IA), is a versatile platform chemical that is produced by Aspergillus terreus using glucose as carbon source. Lignocellulosic biomass can be used as a low cost source of sugars for IA production. However, A. terreus does not produce IA even after 100 fold dilution from enzymatically hydrolyzed wheat straw pretreated with dilute acid. In addition to organic inhibitors, Mn2+ strongly inhibits IA production. Mn2+ was present in the hydrolysate at a level 230 times over the inhibitory limit (50 ppb). Recently, PO43− limitation was shown to decrease the inhibitory effect of Mn2+ on IA production and a medium was formulated in which A. terreus produced IA very efficiently in the presence of Mn2+ up to 100 ppm. Here, the effectiveness of this medium was demonstrated at pilot scale using a stainless steel bioreactor and glucose as the substrate. The productions of IA from corn stover cellulosic hydrolysate in a biorefinery concept and mitigated wheat straw hydrolysate using the Mn2+ tolerant medium were also demonstrated at laboratory scale. The fungal strain produced 74% IA from cellulosic hydrolysate and 98% IA from wheat straw hydrolysate in comparison with respective mock sugar solution. This is the first report on using Mn2+ tolerant medium to achieve IA production by A. terreus on hydrolysates.