The Silk Road, which derives its name from the trade of silk produced by the domestic silkworm Bombyx mori, was an important episode in the development and interaction of human civilizations. However, the detailed history behind silkworm domestication remains ambiguous, and little is known about the underlying genetics with respect to important aspects of its domestication. Here, we reconstruct the domestication processes and identify selective sweeps by sequencing 137 representative silkworm strains. The results present an evolutionary scenario in which silkworms may have been initially domesticated in China as trimoulting lines, then subjected to independent spreads along the Silk Road that gave rise to the development of most local strains, and further improved for modern silk production in Japan and China, having descended from diverse ancestral sources. We find that genes with key roles in nitrogen and amino acid metabolism may have contributed to the promotion of silk production, and that circadian-related genes are generally selected for their adaptation. We additionally identify associations between several candidate genes and important breeding traits, thereby advancing the applicable value of our resources.