Hannah Rankin failed in her bid to win the IBF, WBA and WBC middleweight titles, losing on points to Claressa Shields in Kansas.
The 28-year-old was aiming to become the first female boxer from Scotland to win a world title.
However, American Shields won by unanimous decision to retain her unbeaten record.
All three judges at the Kansas Star Arena and Casino scored the 10-round fight 100-90.
Rankin, from Luss, held her own in the opening round but was rocked by a right hook in the second as Shields began to show her quality.
Shields, 23, continued to dominate with the jab, and again landed a heavy right in the seventh.
A dogged Rankin rallied in the ninth but had to withstand a heavy barrage in the final round as her opponent looked for a knockout.