The incident happened at the Phoenix Sky Harbor International Airport in Arizona.
The woman had vacuum-sealed kilo bricks of fentanyl in her checked bag.
Police said six kilos of powdered fentanyl was seized and 50,000 fentanyl pills.
The luggage did not pass the security screening because an anomaly was found inside.
Airport officers tracked her down and arrested her.
Phoenix police on Tuesday said the woman was traveling from Phoenix to Atlanta.
Her identity was not released. It was not immediately known what charges she would face.