The distribution characteristics of 17 toxic polychlorinated dibenzodioxin/furan (PCDD/F) isomers are closely related to their toxic equivalents, and hence, knowing the transformation and contribution pathways among PCDD/F isomers is the foundation of selectively regulating their isomer emissions. Based on the relevance of PCDD/F isomers, a pathway substitution (PTWS) prediction method among PCDD/F isomers was proposed and employed in this work. First, the accuracy of the PTWS prediction method was confirmed by taking the chemical looping combustion (CLC) of plastic waste (including Fe-based CLC and that with CaO decoration) experimental data as an example and comparing it with the existing position-substitution (PSTS) prediction method. The evaluation indexes include similarity (S), average percentage content error (C), and maximum percentage content error (Z). Second, the effects of CaO decoration on the single chlorine substitution pathway were compared by calculating the chlorine substitution probability. The results show three decreasing chlorine substitution probabilities for the main transformation pathways which are affected by CaO decoration. In addition, the PCDD/F percentage content migration pathway diagrams were drawn to further confirm the critical pathways that affect the distribution of PCDD/F isomers. Finally, the mean toxic equivalent migration situations of PCDD/Fs were calculated according to the toxic equivalents and chlorine substitution probabilities of PCDD/F isomers. The results showed that CaO decoration further reduced the chlorine substitution probability of 1,2,3,7,8-PeCDD, which was identified as the main reason for the increase of the mean toxic equivalents of PCDD, while it slightly altered the mean toxic equivalent for PCDFs. This study can provide a new theoretical basis for further exploring the low PCDD/F emission technology in the CLC process of plastic waste.