Extradiol dioxygenase chemistry is essential for catechol breakdown. The largest natural reservoir of catechols, or 1,2-dihydroxybenzenes, is the plant woody-tissue polymer lignin. Vicinal–oxygen–chelate (VOC) dioxygenases make up the largest group of characterized extradiol dioxygenases, and while most are found as part of catabolic pathways degrading a variety of natural and human-made aromatic rings, L-DOPA (l-3,4-dihydroxyphenylalanine) dioxygenase is a VOC enzyme that participates in the biosynthesis of a natural product. All VOC superfamily members shared conserved elements of catalysis, yet despite decades of investigation of VOC enzymes, the relationships between VOC domain architecture and enzymatic function remain complex and poorly understood. Herein, we present evidence that L-DOPA dioxygenase is the representative member of a new topological class of VOC extradiol dioxygenases. Guided by its evolutionary similarity to glyoxylase enzymes, we performed a careful investigation of the Streptomyces lincolnensis L-DOPA dioxygenase (LmbB1) active site through mutagenesis, kinetic, and pH studies. Our results demonstrate that the L-DOPA dioxygenase reaction depends upon an active-site tyrosine and histidine and is remarkably resilient to mutation, even at the iron-ligating residues. Evaluation of the cleavage reaction as a function of pH supports the role of a histidine in acid–base catalysis. The active-site architecture is functionally consistent with the existing knowledge of VOC extradiol dioxygenase catalysis.