β-Catenin, a key transcriptional factor involved in the canonical Wnt signaling pathway, is regulated by a cascade of phosphorylations and plays a major role in the progression of triple-negative breast cancer (TNBC). However, the phosphorylation induced conformational changes in a β-Catenin is still poorly understood. Hence, we adopted a conventional molecular dynamics approach to study phosphorylations present in a sequence motif Ser 552 675 and Tyr670 of the β-Catenin domain and analyzed in terms of structural transitions, bond formation, and folding-misfolding conformations. Our results unveil the β-Catenin linear motif 549–555 (RRTSMGG) of armadillo repeats domain prefers order to disorder state. In contrast, helix C associated with 670–678 (YKKRLSVEL) motif prefers disorder to order upon phosphorylation of Ser 552 675 and Tyr670. In addition, the crucial secondary structural transition from α-helix to coil induced by phospho Ser552 and phospho Tyr670 of β-Catenin ARM domain connecting helix C modifies conformational diversity and binding affinities of the complex interaction in functional regulation significantly. Moreover, the post phosphorylation disrupted the hydrogen bond interactions (Ser552-Arg549, Arg550-Asp546 and Ser675-Lys672) and abolished the residual alliance with hydrophobic interactions (Tyr670-Leu674) that easily interrupt in secondary structure packing as well as folding conformations connecting ARM and helix C (R10, 12 & R1C) compared to unphosphorylation. Our integrated computational analysis may help in shedding light on understanding the induced folding and unfolding pattern due to motif phosphorylations. Overall, our results provide an atomistic structural description of the way phosphorylation facilitates conformational and dynamic changes in β-Catenin, a fundamental molecular switch mechanism in triple-negative breast cancer pathogenesis. © 2020 Elsevier Inc.