While new art galleries seem to pop up in New York almost weekly these days, it’s equally impressive that some old ones have managed to stick around, adapting to successive eras and sweeping changes in the art market. Beginning on Thursday, James Graham & Sons, a gallery dealing in American painting, American and European sculpture, and contemporary art, will celebrate its 150th anniversary with an exhibition that traces the gallery’s long-term relationships to major artists and clients — the latter including institutions such as the Metropolitan Museum of Art, the Museum of Modern Art, the National Gallery of Art, and the Hirshhorn Museum and Sculpture Garden.

James Graham & Sons is not the oldest gallery in the city — that distinction belongs to Knoedler & Co., founded in 1846 — but it has been in a single family for five generations. It was founded in 1857 by Samuel Graham, a Scottish immigrant, as a furniture and decorative arts business. From its original location in Lower Manhattan, the gallery moved gradually northward along with the city, arriving at its current location on Madison Avenue at 78th Street in 1955.

Today, Graham & Sons is planning another move, to an as-yet-undetermined location, probably in the same neighborhood. Other changes are happening, too, as the representative of the fifth generation, Robert Graham Jr., withdraws from the day-to-day business and hands more responsibility to his partners, who are not Grahams: Cameron Shay and Priscilla Caldwell. “You’re looking at the sixth generation right here,” he said, referring to Mr. Shay and Ms. Caldwell.

Ms. Caldwell, who put together the anniversary exhibition, decided against doing a show of “greatest hits” the gallery has sold — the Winslow Homers, the Edward Hoppers, the Georgia O’Keeffes — in favor of telling a story about relationships with artists like the Wyeths and clients like Joseph Hirshhorn, who donated his collection to the Smithsonian Institution. “We tried to focus on paintings we had sold to museums, and then I put together a wish list,” Ms. Caldwell said. She described the artists in the show as “painters’ painters — it’s esoteric work, not the obvious.”

The exhibition will include about 40 pieces, by artists including John White Alexander, George Bellows, Henry Varnum Poor, and Elaine de Kooning; a companion book reproduces many more works the gallery has sold through its history.

In the early years, “Graham’s,” as it was then called, dealt primarily in furniture and decorative arts. An ad from the late 19th century offered “antiques, rare curiosities, bronzes, curios, mahogany furniture cabinets, Turkey rugs, portieres, Sèvres and Dresden china.”

In the early 20th century, the gallery did a lot of business in silver, reflecting an interest of the third-generation director, James A. Graham. When his son James R. Graham entered the business in the late 1930s, the focus shifted toward painting and sculpture, with a strong emphasis on Western subject matter. The gallery sold a number of important paintings by Frederic Remington and Charles M. Russell, including several to the Texas collector Amon Carter. The Fort Worth museum that houses Carter’s collection and bears his name has lent two paintings back to the gallery for the exhibition.

Since the 1960s, Graham & Sons has distinguished itself by representing artists’ estates and by calling attention to unfairly neglected 19th- or early 20th-century artists. A 1966 exhibition played a substantial role in resurrecting the reputation of John La Farge, a painter and stained-glass designer who was a friend of William and Henry James. For the upcoming exhibition, the National Gallery has lent La Farge’s “Entrance to the Tautira River, Tahiti, Fisherman Spearing a Fish” (c. 1895), which La Farge based on a trip he made to the South Pacific with Henry Adams, and which the National Gallery purchased from Graham & Sons in 1966.

Among the estates the gallery represents are those of Oscar Bluemner, Helen Torr, and Guy Pène du Bois. (MoMA is lending a charcoal drawing by Torr and two Bluemner watercolors, which the Graham family donated to the museum.) The Hirshhorn is lending Pène du Bois’s “Night Club” (1933).

The gallery has had relationships with N.C., Andrew, and Jamie Wyeth, the last of whom the gallery represented for seven years. The exhibition will include two paintings each by N.C. and Andrew Wyeth.

Today, the primary challenge for Graham & Sons, the partners said, is one faced by many galleries: finding enough material to satisfy the intense demand. “One of my favorite stupid sayings is: ‘There are no more 19th -century artists doing good work today,'” Mr. Graham joked, adding that the same will soon be true of 20th-century artists.

The number of people collecting art has risen dramatically, he said, making supply a problem. “It’s very frustrating,” Mr. Graham said. “When I first came into the business, there was a wonderful group of collectors — the Fraads and the Spencers and the Horowitzes were the well-known ones here in the city — and they did the Saturday promenade of the galleries that dealt in American paintings. Every week they would come in and ask ‘What’s new?’ and you would show them the new Homer or [John Henry] Twachtman or the new painting by one of The Eight” — a group of American proto-modernists that included William Glackens, Everett Shinn, John Sloan, and Maurice Prendergast. “If we get one of those new pictures twice a year now we’re happy, and back then you had all you could sell.”

The gallery’s contemporary department, now run by Jay Grimm, will also be represented in the exhibition, with new works by two of its artists, Stephen Hannock and Nancy Lorenz. Mr. Grimm said the contemporary program is not simply an offshoot of the other departments. “In the context of an uptown gallery doing American art, people might expect us to show Neo Hudson River School work, but I’m not into that,” he said. “I’d like to think I’m showing good contemporary work that engages concerns of the present.”