Best known for figures from her own life and those beyond it, including close friends, historical personae, and icons of contemporary culture, Peyton's portraits have regularly featured artists, writers, musicians, and actors.

Peyton's artwork, mainly figurative, can be characterized by a coupling of understatement and intensity, depicting subjects from her own life and beyond with both startling immediacy and her signature richly modulated surfaces.

[3][4] Peyton draws much inspiration from the creative work of historical figures like Gustave Flaubert and John Singer Sargent, and she has expressed that she is part of a lineage of artists and writers like Balzac, Camille Claudel, Delacroix, Isa Genzken, Giorgione, Georgia O'Keeffe, etc.

[7] In her interview with Frieze magazine, Peyton expressed that when she chooses to paint from another artist's work, it allows her to explore "harder-to-reach things inside herself" because the composition is already decided.

Examples featured in Peyton's 2017 Dark Incandescence monograph include Pati (2007), Balzac + Roses (2008), Flaubert + Madame Bovary (Elephants) (2008), Camille Claudel and Flowers (Still Life) (2009), Actaeon, Justin Bieber and Grey Roses (2010), Flowers, Lichtenstein, Parsifal (2011), Berlin, Hyacinth and Black Teapot (2014), and Universe of the World-Breath (2018).

This first survey of Peyton's work in an American institution included her latest portraits, which revealed a greater emphasis on the psychology of subjects such as Matthew Barney and John Giorno.

[16] Her work has also been the subject of solo exhibitions at the Royal Academy in London (2002); Salzburger Kunstverein, Salzburg, Austria (2002); Deichtorhallen, Hamburg, Germany; Irish Museum of Modern Art (2009); Guild Hall, Easthampton, New York (2006); Aldrich Contemporary Art Museum, Ridgefield, Connecticut (2008); Mildred Lane Kemper Art Museum, where Ghost: Elizabeth Peyton, a retrospective of the artist's prints, was presented concurrently with the same exhibition at the Opelvillen in Rüsselsheim, Germany (2011); Metropolitan Opera, New York (2011 and 2016).

[18] In 2017, the Villa Medici in Rome exhibited Elizabeth Peyton & Camille Claudel: Eternal Idol in which works by the artists, born a century apart, are shown alongside each other, creating a dialogue between their distinct approaches to portraiture.