To unravel the nature of band gap engineering of adsorption energy, we investigated the adsorption of H and CO on two-dimensional two-layer (2L)- and three-layer (3L)-TiO2(110) semiconductors by density functional theory calculations. Molecular orbital theory was used to develop a new H–O bonding mechanism. We propose that the H 1s orbital combines linearly with the occupied σO–Tibonding orbital to form σH–OTibonding and σ*H–OTiantibonding orbitals. Two of three electrons (one from H and two from σO–Ti) fill the σH–OTibonding orbital, and the other electron fills the pristine lowest unoccupied σ*O–Tiorbital rather than σ*H–OTi. Consequently, the H adsorption energy EH-adsis decided by the stabilization energies ΔEAB(occupation of σH–OTi) and ΔEe(lowered energy due to electron filling of σ*O–Ti) and the destabilization energy ΔEAB(occupation of σ*O–Ti). The stabilization energies for H adsorption on the 2L and 3L are similar; therefore, the EH-adsdifference is predominantly determined by the corresponding ΔEAB, which is dominated by the 2L and 3L band gaps. The C–O bonding mechanism is similar. This mechanism for surface chemical bonding shows the critical role of the band gap in determining the adsorption energy and provides a theoretical basis for band gap engineering in heterogeneous catalysis.