Unique heme-containing tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) catalyze oxidative cleavage of the pyrrole ring of L-tryptophan (Trp). Although these two heme dioxygenases were discovered more than 40 years ago, their reaction mechanisms were still poorly understood. Encouraged by recent X-ray crystal structures, new mechanistic pathways were proposed. We performed ONIOM(B3LYP:Amber) calculations with explicit consideration of the protein environment to study various possible reaction mechanisms for bacterial TDO. The ONIOM calculations do not support the proposed mechanisms (via either formation of the dioxetane intermediate or Criegee-type rearrangement); a mechanism that is exceptional in the hemes emerges. It starts with (1) direct radical addition of a ferric-superoxide intermediate with C2 of the indole of Trp, followed by (2) ring-closure via homolytic O-O cleavage to give epoxide and ferryl-oxo (Cpd II) intermediates, (3) acid-catalyzed regiospecific ring-opening of the epoxide, (4) oxo-attack, and (5) finally C-C bond cleavage concerted with back proton transfer. The involvement of dual oxidants, ferric-superoxide and ferryl-oxo (Cpd II) intermediates, is proposed to be responsible for the dioxygenase reactivity in bacterial TDO. In particular, the not-well-recognized ferric-superoxide porphyrin intermediate is found to be capable of reacting with pi-systems via direct radical addition, an uncommon dioxygen activation in the hemes. The comparison between Xanthomonas campestris TDO and some heme as well non-heme oxygenases is also discussed.