Among the known aromatic N-heterocycles, pyrroles are significant and versatile privileged components in pharmacologically relevant molecules. Herein, we demonstrate a protocol for the selective construction of alkynylated pyrroles in a diversity-oriented fashion through divergent C2/C5 site-selective alkynylation of pyrrole derivatives by employing a palladium catalyst with two different solvent systems. In the presence of 1,4-dioxane, the C2-alkynylation process via chelation-assisted palladation is favored. However, the use of a dimethylformamide/dimethyl sulfoxide (DMF/DMSO) solvent system could override the chelation effect of a weak ester-directing group, favoring the C5-alkynylation process via electrophilic palladation. Late-stage modification of biologically relevant scaffolds and further derivatization of the products highlighted the potential utility and importance of the solvent-controlled regiodivergence.