The American art collection at the High features significant works by renowned nineteenth- and twentieth-century American artists such as William Merritt Chase, Childe Hassam, Henry Ossawa Tanner, John Twachtman, Marsden Hartley, and Andrew Wyeth.

It includes landscapes by Hudson River School artists, figure paintings by Henry Inman and John Singer Sargent, and still-life paintings by John Frederick Peto, William Michael Harnett, and William Mason Brown.

Recent acquisitions have focused on American painting and sculpture of the late nineteenth century as well as twentieth-century modernism with works by artists ranging from painters Benjamin West, Frederic Edwin Church, and John Singer Sargent and the sculptor Edmonia Lewis to such influential modernists as Joseph Stella, Georgia O'Keeffe, and John Marin, bringing the American collection to more than 1,000 objects.