We explore here a long-standing mechanistic question by using quantum-mechanical/molecular-mechanical (QM/MM) methodology. The question concerns the mechanism of steroid hormone biosynthesis, whereby the P450 enzyme, CYP11A1, catalyzes the C20-C22 bond-cleavage in the 20,22-hydroxylated cholesterol, 20R,22R-DiOHCH, leading to pregnenolone, which is critical for the subsequent production of all steroid hormones. This is an unusual feat whereby the P450 enzyme breaks two O-H bonds and one C-C bond, while making two C═O bonds. How does the enzyme perform such a complex and highly energy-demanding reaction? Our computational results rule out the previously proposed Compound I (Cpd I) electrophilic attack mechanism via the formation of a peroxide intermediate as well as the H-abstraction-mediated C-C cleavage mechanism. Notably, oxygen-rebound cannot transpire, in spite of the fact that the classical active species, Cpd I, participates in the catalytic process. Our findings reveal a mechanism whereby C-C bond cleavage is mediated by an electron transfer from the C22-O--deprotonated substrate to Cpd I. As such, our QM/MM calculations demonstrate that Cpd I acts as an electron sink that facilitates the C-C bond cleavage.