Mechanistic assessments based on kinetic and isotopic methods combined with density functional theory are used to probe the diverse pathways by which C-H bonds in CH4 react on bare Pd clusters, Pd cluster surfaces saturated with chemisorbed oxygen (O*), and PdO clusters. C-H activation routes change from oxidative addition to H-abstraction and then to sigma-bond metathesis with increasing O-content, as active sites evolve from metal atom pairs (*-*) to oxygen atom (O*-O*) pairs and ultimately to Pd cation-lattice oxygen pairs (Pd2+-O2-) in PdO. The charges in the CH3 and H moieties along the reaction coordinate depend on the accessibility and chemical state of the Pd and O centers involved. Homolytic C-H dissociation prevails on bare (*-*) and O*-covered surfaces (O*-O*), while C-H bonds cleave heterolytically on Pd2+-O2- pairs at PdO surfaces. On bare surfaces, C-H bonds cleave via oxidative addition, involving Pd atom insertion into the C-H bond with electron backdonation from Pd to C-H antibonding states and the formation of tight three-center (H3C center dot center dot center dot Pd center dot center dot center dot H)double dagger transition states. On O*-saturated Pd surfaces, C-H bonds cleave homolytically on O*-O* pairs to form radical-like CH3 species and nearly formed O-H bonds at a transition state (O*center dot center dot center dot CH3 center dot center dot center dot center dot*OH)double dagger that is looser and higher in enthalpy than on bare Pd surfaces. On PdO surfaces, site pairs consisting of exposed Pd2+ and vicinal O2-, Pd-ox-O-ox, cleave C-H bonds heterolytically via sigma-bond metathesis, with Pd2+ adding to the C-H bond, while O2- abstracts the H-atom to form a four-center (H3C delta-center dot center dot center dot Pd-ox center dot center dot center dot H delta+center dot center dot center dot O-ox)double dagger transition state without detectable Pd-ox reduction. The latter is much more stable than transition states on *-* and O*-O* pairs and give rise to a large increase in CH4 oxidation turnover rates at oxygen chemical potentials leading to Pd to PdO transitions. These distinct mechanistic pathways for C-H bond activation, inferred from theory and experiment, resemble those prevalent on organometallic complexes. Metal centers present on surfaces as well as in homogeneous complexes act as both nucleophile and electrophile in oxidative additions, ligands (e.g., O* on surfaces) abstract H-atoms via reductive deprotonation of C-H bonds, and metal-ligand pairs, with the pair as electrophlle and the metal as nucleophile, mediate sigma-bond metathesis pathways.