It has been shown previously that the thermoelectric properties of the Zintl phase compound, YbZn2Sb2 can be finely tuned via substitution at the cationic Yb-site. Here we report the results of the investigation of isoelectronic substitution of Zn by Mn in the anionic (Zn2Sb2)2- framework. The p-type YbZn2-xMnxSb2 (0.0≤x≤0.4) samples have been synthesized via a solid-state reaction followed by suitable cooling, annealing, grounding, and hot-pressing densification processes. In samples with x=0.0, 0.05, 0.10, 0.15, 0.2, 0.3, and 0.4, the electrical conductivity, Seebeck coefficient, and thermal conductivity measurements have been performed as a function of temperature from 300 to 750 K. It is found that the Mn substitution effectively lowers the thermal conductivity for all samples, while it significantly increases the power factor for x≤0.15. As a result, a dimensionless figure of merit ZT of ∼0.61–0.65 has been attained at 726 K for x=0.05–0.15 as compared to the ZT of ∼0.48 in the unsubstituted YbZn2Sb2.