Recognized for her paintings of friends, family, lovers, poets, artists, and strangers, Neel is considered one of the greatest American portraitists of the 20th century.

She pursued a career as a figurative painter during a period when abstraction was favored, and she did not begin to gain critical praise for her work until the 1960s.

In 1918, after graduating from high school, she took the civil service exam and got a high-paying clerical position in order to help support her parents.

[15] At Philadelphia School of Design for Women, she won honorable mention in her painting class for the Francisca Naiade Balano Prize two years in a row.

[6][12] In 1924, Neel met Carlos Enríquez, an upper-class Cuban painter, at the Chester Springs summer school run by PAFA.

This exhibition also included Eduardo Abela, Víctor Manuel García Valdés, Marcelo Pogolotti, and Amelia Peláez who were all part of the Cuban Vanguardia Movement.

[6] The trauma caused by Santillana's death infused the content of Neel's paintings, setting a precedent for the themes of motherhood, loss, and anxiety that permeated her work for the duration of her career.

During the time of Enriquez's absence, Neel sublet her New York apartment and traveled to work in the studio of her friends and fellow painters Ethel V. Ashton and Rhonda Myers.

[21] At the end of 1933, Neel was offered $30 a week to participate in the Public Works of Art Project (PWAP) during an interview at the Whitney Museum.

While enrolled in these government programs she painted in a realist style and her subjects were mostly Depression-era street scenes and Communist thinkers and leaders.

[15] Her work glorified subversion and sexuality, depicting whimsical scenes of lovers and nudes, like a watercolor she made in 1935, Alice Neel and John Rothschild in the Bathroom, which showed the naked pair peeing.

[6] In the 1930s, Neel gained a reputation as an artist, and established a good standing within her circle of downtown intellectuals and Communist Party leaders.

While Neel was never an official Communist Party member, her affiliation and sympathy with the ideals of Communism remained constant.

[21] Neel's subject matter changed; she went from painting portraits of ordinary people, family, friends, strangers, and well-known art critics to female nudes.

The female nude in Western art had always represented a "Woman" as vulnerable, anonymous, passive, and ageless and the quintessential object of the male gaze.

"[27] The formal elements of the painting, light and shadow, the brushstrokes, and the color are suggested to add pathos and humor to the work but they are done in a precise manner to convey a certain tone, which is vulnerability.

For this reason she thought of herself as a realist painter.Neel's second son, Hartley, was born in 1941 to Neel and her lover, the communist intellectual Sam Brody.

During the 1940s, Neel made illustrations for the Communist publication Masses & Mainstream, and continued to paint portraits from her uptown home.

In the 1950s, her friendship with Mike Gold and his admiration for her social realist work garnered her a show at the Communist-inspired New Playwrights Theatre.

I feel as a subject it's perfectly legitimate, and people out of a false modesty, or being sissies, never show it, but it is a basic fact of life.

[32] Margaret was painted while sitting on upright chair that forced her to expose her pregnant stomach even more, which became the central point in the canvas.

[33] Pamela Allara says Neel has been accurately characterized as a "sort of artist–sociologist who revived and redirected the dying genre of ameliorative portraiture by merging objectivity with subjectivity, realism with expressionism.

In visually interpreting a person's habitus, Neel understood that she could not be an objective observer, that her depictions would of necessity include her own response.

However, she was encouraged by her son Richard to complete it and came back to in her early 80s as she was also invited to take part in an exhibition of self-portraits at the Harold Reed Gallery in New York.

[6] In 2010, Jeremy Lewison and Barry Walker presented, for Museum of Fine Arts, Houston, Alice Neel: Painted Truths, on view from March 21 to June 15, 2010,[46] which later went to the Whitechapel Gallery, London and Moderna Museet Malmö, Sweden.

[47][48] In 2013, the first major presentation of the artist's watercolors and drawings, as Alice Neel: Intimate Relations, was on view at Nordiska Akvarellmuseet in Skärhamn, Sweden.

[47] In 2016, the Ateneum, Helsinki presented Alice Neel: Painter of Modern Life, which later went to the Kunstmuseum Den Haag, The Hague, the Fondation Vincent van Gogh Arles, France, and, in 2018, the Deichtorhallen, Hamburg, Germany, from October 10, 2017, to January 14, 2018.

[47][50] In 2017, Hilton Als curated the exhibition "Alice Neel, Uptown" at the Victoria Miro Gallery in London (May 18 – July 29, 2017).

[55][56] In 2023, Alice Neel: Hot Off The Griddle, the largest exhibition of her work to date in the UK, opened at The Barbican Centre Art Gallery in London running from 16 February until 21 May 2023.

[57][58][59][60] In 2024, Alice Neel: At Home, curated by Hilton Als, was the first major exhibition to focus on queer communities and those who were part of her circle, opened at David Zwirner Gallery.