The Mo(PMe3)6-catalyzed C–S cleavage of thiophene was studied using density functional theory (DFT). A comparison of several possible pathways shows that, the five- and four-coordinated species are determined as two most active catalyst species, and this reaction is the most likely to undergo consecutively the dissociation of two PMe3 groups from Mo(PMe3)6 to give the four-coordinated Mo(PMe3)4, the binding of thiophene to Mo(PMe3)4 in η1-S-mode to give Mo(PMe3)4(η1-S-thiophene), the transformation of Mo(PMe3)4(η1-S-thiophene) into the Mo(PMe3)4(η2-C2,S-thiophene), and the cleavage of the C–S bond of thiophene to give the ring-opened species Mo(PMe3)4(κ2-C2,S-thiophene). The butadiene–thiolate complex (η5-C4H5S)Mo(PMe3)2(η2-CH2PMe2) may generate in the ring-opened species through the departure of one PMe3 group, hydrogen transfer and structural transformation. The thiophene adduct Mo(PMe3)3(η5-thiophene) may originate in Mo(PMe3)4(η2-C2,C3-thiophene) by removing one PMe3 group and changing the η2-coordination mode into η5-coordination mode. The highest formation energy barrier of the thiophene adduct and butadiene–thiolate complex is 20 and 10.4 kcal/mol, respectively, which is easy to cross and supports the facts that the two species can be experimentally observed.