Though he considered himself to be an "abstractionist," Wyeth was primarily a realist painter who worked in a regionalist style, often painting the land and people of his hometown in Chadds Ford, Pennsylvania and his summer home in Cushing, Maine.

N.C. Wyeth gave Andrew art lessons as a child, during which he developed the skills to create landscapes, illustrations, figures, and watercolor paintings.

His influences included the landscape artist Winslow Homer, American philosopher and naturalist Henry David Thoreau, and filmmaker King Vidor.

In addition to being awarded the Congressional Gold Medal in 1988, Wyeth was the first painter to receive the Presidential Medal of Freedom, the first American artist since John Singer Sargent to be elected to the French Académie des Beaux-Arts, and the first living United States artist to be elected to Britain's Royal Academy.

Like his father, the young Wyeth read and appreciated the poetry of Robert Frost and the writings of Henry David Thoreau and studied their relationships with nature.

Vidor later made a documentary, The Metaphor, where he and Wyeth discuss the influence of the film on his paintings, including Winter 1946, Snow Flurries, Portrait of Ralph Kline and Afternoon Flight of a Boy up a Tree.

[7] By the time he was a teenager, his father, N. C. Wyeth, brought him into his studio for the only art lessons he ever had and inspired his son's love of rural landscapes, sense of romance, and artistic traditions.

[7] With his father's guidance, he mastered figure study and watercolor, and later learned egg tempera from his brother-in-law Peter Hurd.

N. C. wrote in a letter to Wyeth in 1944:[8] The great men Thoreau, Goethe, Emerson, Tolstoy forever radiate a sharp sense of that profound requirement of an artist, to fully understand that consequences of what he creates are unimportant.

Wyeth referred to his father's death as a formative emotional event in his artistic career, in addition to being a personal tragedy.

[16] In his art, Wyeth's favorite subjects were the land and people around him, both in his hometown of Chadds Ford, Pennsylvania, and at his summer home in Cushing, Maine.

[7][17] In 1958, Andrew and Betsy Wyeth purchased and restored "The Mill", a group of 18th-century buildings that appeared often in his work, including Night Sleeper (1979, private collection).

[15] Wyeth painted Winter 1946 (1946, North Carolina Museum of Art, Raleigh, 1946), which depicts a neighbor boy, Allan Lynch, running aimlessly down a bleak hill, his hand reaching out.

Wyeth was inspired by Christina, who, crippled from (undiagnosed) Charcot–Marie–Tooth disease, a genetic polyneuropathy, and unable to walk, spent most of her time at home.

Andrew Wyeth painted the church in several landscapes during its active period, and the abandoned building walls appear in Ring Road (1985).

[28] In 1986, extensive coverage was given to the revelation of a series of 247 studies of the German-born Helga Testorf, whom Wyeth met while she was attending to Karl Kuerner at his farm.

[19] Helga, a caregiver with nursing experience, had never modeled before but quickly became comfortable with the long periods of posing, during which he observed and painted her in intimate detail.

[19] She is nearly always portrayed as unsmiling and passive; yet, within those deliberate limitations, Wyeth manages to convey subtle qualities of character and mood, as he does in many of his best portraits.

[30] The show was "lambasted" as an "absurd error" by John Russell and an "essentially tasteless endeavor" by Jack Flam, coming to be viewed by some people as "a traumatic event for the museum.

"[32] The tour was criticized after the fact because, after it ended, the pictures' owner sold his entire cache to a Japanese company, a transaction characterized by Christopher Benfey as "crass.

The National Gallery of Art states that the windows artwork "offer[s] the clearest understanding of Wyeth's creative process"[34] because his paintings of people inspire questions about who the person is and what they are doing.

A west wind filled the dusty, frayed lace curtains and the delicate crocheted birds began to flutter and fly.

[15] Garret Room, a painting of Wyeth's friend Tom Clark, (1962, private collection) was begun in watercolor and finished with the drybrush technique.

It was through painting him, though, that Wyeth understood that, beneath his humor and hard countenance, Cline was a warm-hearted veteran of great dignity and intellect.

[10] When Christina Olson died in the winter of 1969, Wyeth refocused his artistic attention upon Siri Erickson, capturing her naked innocence in The Sauna.

[7] Maidenhair (1974, Andrew and Betsy Wyeth collection), a tempera painting of a lone female figure sitting in a church pew at the Old German Meeting House in Waldoboro, Maine.

[40] Admirers of Wyeth's art believe that his paintings, in addition to their pictorial formal beauty, contain strong emotional currents, symbolic content, and underlying abstraction.

[41] Christina's World became an iconic image, a status unmet to even the best paintings, "that registers as an emotional and cultural reference point in the minds of millions.

"[40] Wyeth created work in sharp contrast to abstraction, which gained currency in American art and critical thinking in the middle of the 20th century.

[40] Museum exhibitions of Wyeth's paintings have set attendance records, but many art critics have evaluated his work less favorably.