The efficiency of thermoelectric (TE) technology relies on the performance of TE materials. Substitution with heavy elements is an effective strategy in TE for enhancing phonon scattering without much affecting electrical transport properties. However, selecting suitable dopants to achieve a high thermoelectric figure-of-merit (ZT) poses a significant challenge. Thus, in this study, the efficacy of combined (Fe and Bi) co-substitution in CrSb2 is investigated as a promising strategy to enhance ZT by lowering thermal conductivity. A series of co-doped Cr1-xFexBiySb2-y (x = 0, 0.25, 0.50, 0.75, 1 and y = 0.10, 0.15, 0.20,0.25) samples were synthesized via furnace reaction followed by spark plasma sintering technique. Phase analysis and temperature dependence TE transport properties were systematically studied on synthesized samples. Furthermore, to analyze the impact of disorder induced by Bi/Fe substitution, electronic structure calculation was performed using the projector augmented-wave method. Notably, Cr0.75Fe0.25Bi0.15Sb1.85 exhibited a low thermal conductivity of ~ 2.5 W m-1 K-1 at 300 K, which reduced to half compared to that of pristine CrSb2 (~ 5 W m-1 K-1). This reduction is attributed to the introduction of significant mass fluctuations and point defects along with the presence of Bi at grain boundaries by co-substitution. Consequently, a remarkable 90% enhancement in ZT (~0.021) at 350 K was achieved for Cr0.75Fe0.25Bi0.15Sb1.85 compared to that of pristine CrSb2 (ZT~0.012). This study can provide valuable insights into the rational design of effective dopants in other TE materials also.