Diageo is selling 19 spirits brands, including Seagrams VO Canadian whisky and cinnamon schnapps Goldschlager, to US-based company Sazerac for $550m.
The deal comes as the company focuses on its premium whisky brands such as Johnnie Walker in the US.
Diageo, which owns Guinness and Smirnoff vodka, said it would return the net proceeds of about £340m to shareholders through a share repurchase.
Sky News reported in May that the company was in talks to sell some US-focused brands for an overall price tag of between $500m and $1 billion.
The sale, which also includes whisky brands such as Seagram's 83, Seagram's Five Star and Jamaican rum Myers's, will reduce Diageo's pre-exceptional earnings per share by 1.9 pence per share in the first full financial year after closing.
"The disposal of these brands enables us to have even greater focus on the faster growing premium and above brands in the US spirits portfolio," the company said in a statement.
The North American region is the biggest market for premium drinks in the world, and accounts for a third of the company's sales and nearly half its operating profit.
Diageo has been expanding the reach and improving the marketing of premium, global brands like Johnnie Walker.
US liquor sales hit a record $26.2 billion in 2017, fuelled by high-end brown liquor and a big thirst for tequila and vodka, an industry group, the Distilled Spirits Council, said in February.
The council, which represents companies such as Diageo, Pernod Ricard and Brown-Forman, had then said higher volumes reflected millennials' taste for high-end and super-premium blended scotch and whisky products.
Diageo said it expects the sale to close in early 2019 and to bring in a one-time gain of roughly £110m.
The company has also agreed to long-term supply contracts with Louisiana, U.S.-based Sazerac.
Sazerac, which traces its roots to the early 19th century, is an independent, family owned company in the US, home to brands such as Buffalo Trace and Pappy Van Winkle bourbon.