Cincinnati will become the 27th US destination served directly from London by the carrier, which offers 300 transatlantic flights per week.
The flight will operate five times per week in the summer season and four in the winter.
The non-stop service was described as an "all-around win" for the Ohio, Kentucky, and Indiana region by Candace McGraw, chief executive officer of Cincinnati/Northern Kentucky airport (CVG).
"The economic impact of this transatlantic flight is exponential for business travel, economic development, and tourism between the UK and our area of the United States," she added.