Henry Walters was noted as an art collector and philanthropist, a founder of the Walters Art Gallery in Baltimore, Maryland, which he donated to the city in his 1931 will for the benefit of the public. From the late 19th century, Walters lived most of the time in New York City, where from 1903 on, he served on the executive committee of the Metropolitan Museum of Art in Manhattan on Fifth Avenue. He was selected as second vice president in 1913, a position he held until his death.
Like his father William Thompson Walters, he was a businessman in the railroad industry, serving as president of the Atlantic Coast Line Railroad, which had been established by his father.