Structural transformations in extended solids result from local atomic rearrangements and phase growth mechanisms. A broad class of technologically relevant properties critically depends on local structural issues connected with domain sizes, domain boundary geometries, and defects. However, a precise understanding of structural transformation mechanisms and domain formation is still an open question. Here, we demonstrate the feasibility of very detailed mechanistic investigations in real materials as a prerequisite for intelligent property control. We address the problem of domain fragmentation in bulk CdSe under pressure, jointly by molecular dynamics simulations, high-pressure experiments, and HR-TEM imaging. We show that domain fragmentation is taking place in the high-pressure regime, where nucleation events generate both zinc blende (B3) and wurtzite (B4) structural motifs and, in turn, cause the final lamellar appearance observable by high-resolution TEM. A changed nucleation pattern and a modified B3/B4 ratio represents the system's response to modified external stress conditions.