The effects of elemental substitutions at the Tl site of a Tl1−xXx(Ba, Sr)CaCu2O7superconductor with X = Cr, Bi, Pb, Se, and Te were investigated. This study aimed to determine the elements that enhance and suppress the superconducting transition temperature of the Tl1−xXx(Ba, Sr)CaCu2O7(Tl-1212) phase. The selected elements belong to the groups of transition metal, post-transition metal, non-metal, and metalloid. The relationship between the transition temperature and ionic radius of the elements was also discussed. The samples were prepared by the solid-state reaction method. The XRD patterns showed a single Tl-1212 phase was formed in the non- and Cr-substituted (x= 0.15) samples. The Cr-substituted samples (x= 0.4) showed a plate-like structure with smaller voids. The highest superconducting transition temperatures (Tc onset,Tcχ′, andTp) were also achieved by the Cr-substituted samples forx= 0.4 compositions. However, the substitution of Te suppressed the superconductivity of the Tl-1212 phase.Jc inter(Tp) for all samples was calculated to be in the range of 12–17 A/cm2. This work shows that substitution elements with a smaller ionic radius tend to be more favorable in improving the superconducting properties of the Tl-1212 phase.