Blessed thistle is an important medicinal crop in Europe and recently has become more significant in North America. A limiting factor in blessed thistle production is weed interference. Field experiments were conducted near Plovdiv, Bulgaria, to study the effect of selected herbicides on weed control, crop productivity, and crop quality. Seed yields of blessed thistle were increased with metribuzin alone at 0.5 kg ai/ha, pendimethalin alone 1.32 kg ai/ha, pendimethalin at 1.32 kg ai/ha plus metribuzin at 0.5 kg ai/ha, trifluralin at 0.84 kg ai/ha plus linuron at 1.0 kg ai/ha, and in the hand-weeded control compared to the nonweeded control (nontreated check). Pendimethalin and metribuzin were safe both alone and in combination for weed control in blessed thistle. Bentazon at 0.96 kg ai/ha inhibited blessed thistle development and reduced seed yields compared to the untreated check. Generally, weed control increased the content of silymarin and decreased the amount of seed oil. Overall, seeds contained 0.26 to 0.36% taxifolin, 0.69 to 0.99% silydianin plus silycristin, 1.31 to 1.78% silybin, and 0.27 to 0.39 % isosilybin.