Thermoelectric properties of n-type LnTSbO (Ln = lanthanides and T = Zn, Mn) were firstly investigated by the first-principles method and the semi-classical Boltzmann theory. The results show that a multiple-valley structure appears around the bottom of conduction band. The valley with a high band degeneracy consists of the bands with a weak band dispersion, leading to large magnitudes of the Seebeck coefficient but low electrical conductivity. The valley with a low band degeneracy is made up of the bands with an intense band dispersion, resulting in a high electrical conductivity but small magnitudes of the Seebeck coefficient. The thermoelectric properties are dominated by the energy difference, ΔE, between the valleys. The ΔE value of LnZnSbO linearly increases with the ionic radius of Ln. The thermoelectric properties are thus effectively modulated by varying the lanthanides. As a result, LnZnSbO (Ln = Ce-Nd) with the moderate values of ΔE shows a better thermoelectric performance. The multiple-valley effect is an effective way to modulate the thermoelectric properties of n-type LnTSbO.