The Brothers' works from 1979 to the present show a wide range of often esoteric influences, starting with the Polish animators Walerian Borowczyk and Jan Lenica and continuing with the writers Franz Kafka, Bruno Schulz, Robert Walser and Michel de Ghelderode, puppeteers Wladyslaw Starewicz and Czech Richard Teschner and Czech composers Leoš Janáček, Zdeněk Liška and Polish Leszek Jankowski, the last of whom has created many original scores for their work.

[4] In a panel discussion with Daniel Bird and Andrzej Klimowski at the Aurora festival in Norwich, they emphasized that a more significant influence on their work was Walerian Borowczyk, who made both animation shorts and live-action features.

Most of their animation films feature puppets made of doll parts and other organic and inorganic materials, often partially disassembled, in a dark, moody atmosphere.

[7] They have created music videos for His Name Is Alive ("Are We Still Married", "Can't Go Wrong Without You"), Michael Penn ("Long Way Down (Look What the Cat Drug In)") and 16 Horsepower ("Black Soul Choir").

Although they worked on Peter Gabriel's seminal video "Sledgehammer" (1986) as animators, this was directed by Stephen R. Johnson and the Quay Brothers in order to support their personal projects.

After designing book covers for Gothic and science fiction books while in Philadelphia, the Quay Brothers have created suggestive designs for a variety of publications that seem to reflect not only their own interests in particular authors, covers for Italo Calvino, Louis-Ferdinand Céline or Mark le Fanu's study of the films of Andrei Tarkovsky, but also in themes and motifs that these authors develop.

Literary texts are inspirational sources for almost all of their film projects, whether they serve as a point of departure for their own ideas or as a textual basis for filmic scenarios, and not as scripts or screenplays.

The prowess in illustration and calligraphy seeps increasingly into many formal elements in their later films, evident as graphic embellishment in the set decoration, or their particular use of patterns in the puppets' costume design.

In an interview with Robert K. Elder for his book The Best Film You've Never Seen, the Quay Brothers discuss their creative process, stating: "If [a] project does eventually get approval, then we almost invariably chuck [the] original proposal out, not out of any cavalierness, but simply because we know that, as we start building the decors and the puppets, the script begins to grow and evolve very organically.

Their work at miniature scale has translated into large-scale designs for the theatre and opera productions of director Richard Jones: Prokofiev's The Love for Three Oranges; Feydeau's "A Flea in Her Ear"; Tchaikovsky's Mazeppa; and Molière's "Le Bourgeois Gentilhomme".

The Quay Brothers produced a new film entitled Through the Weeping Glass: On the Consolations of Life Everlasting (Limbos & Afterbreezes in the Mütter Museum).

The production was overseen by Edward Waisnis through PRO BONO films, in collaboration with Atelier Koninck QBFZ, and the support of the Fundación Felisberto Hernández, and features a score composed by Timothy Nelson, who has worked with the Quay Brothers previously.

Hollywood director Christopher Nolan revealed himself to have been an admirer of the Quay Brothers' work since coming across their films late at night when they were originally screened on Channel 4 in the UK.

In 2015, Nolan curated a theatrical tour showcasing newly restored 35mm prints of the Quay's films In Absentia, The Comb and Street of Crocodiles.