Mitchell grew up in a culturally oriented family. Her mother was a poet and editor, and her father an amateur artist. As a child, Mitchell frequently visited the Art Institute of Chicago and the Field Museum with her father, where they would draw and paint watercolors, and she later received her BFA and MFA from the School of the Art Institute. Although Mitchell moved to New York after the completion of her studies, she would later title several works in reference to her hometown, and frequently mentioned its continued influence on her sensibility and work. Her love of poetry and of nineteenth-century French paintings— which took root in the galleries of the Art Institute of Chicago—remained steadfast passions throughout her life.

Mitchell’s St. Mark’s Place studio was a simple space—one large room divided into two areas—and organized around her painting practice. The studio's windows faced north, and she often painted on large, unstretched canvases stapled to the wall. In the midst of her active social and professional life, she prized the privacy of this studio and would later recall: "St. Mark's has always stayed a place that nobody invaded except George, my poodle. Nobody moved in on me there. It still is an enormous thing to me."

Mitchell's first solo exhibition in New York was at the New Gallery in 1952, and soon after she gained representation by the Stable Gallery, where her work was shown in solo and group exhibitions until 1965. Mitchell retained gallery representation in New York throughout her career (showing with Martha Jackson Gallery, Xavier Fourcade, and Robert Miller Gallery), and returned to New York from France regularly for exhibitions, and to visit with friends.

Paris

Mitchell’s first sojourn in Paris, in 1948, was supported by a traveling fellowship from the School of the Art Institute of Chicago. In the wake of the Second World War, she found the city devastated, though she managed to rent a studio (with barebones plumbing and electricity) on the rue Galande, in the fifth arrondissement. She wrote to her then boyfriend Barney Rosset "J’ai un atelier – [...] from my window I can see Notre Dame – [...] It has 2 enormous windows – north light – white, white walls." Mitchell's stay in this apartment, though productive, was brief. The damp cold of winter made her ill, so she left Paris for the south of France at the end of 1948.

Mitchell returned to Paris in 1955, and lived between Paris and New York until 1959. During this period, she lived and painted in eight different temporary Parisian studios, which was logistically challenging and imposed various constraints on her work.

Vétheuil

Mitchell acquired La Tour, her home in Vétheuil, France, in 1967, and moved there permanently in late 1968, following extensive renovations. Nestled against a hillside in this small town approximately 70 kilometers northwest of Paris, Mitchell's property included lush gardens and fruit trees, as well as a separate structure (formerly a game pavilion) at the top of the hill, which she converted to a studio. The home had extraordinary views of a twelfth century Gothic church to the southeast, beyond Mitchell's vegetable garden, and of the Seine River, homes in the village of Lavacourt (just across the Seine), and surrounding lakes and distant fields to the west. In a witty allusion to Vermeer, she described this landscape as her "View of Delft."

Although surrounded by a breathtaking landscape, the west-facing windows of this studio were covered with burlap, and Mitchell largely worked at night. She chose to work in what she referred to as “electric light,” checking her paintings in daylight the following day.

Near the end of her life, Mitchell reflected: "The solitude that I find in my studio is one of plenitude. I am enough for myself, I am fully there." Mitchell worked in her Vétheuil studio continuously from 1968 until her death in 1992.