Collaborators of Orpheus include Fazıl Say, Isaac Stern, Gidon Kremer, Itzhak Perlman, Gil Shaham, Yo-Yo Ma, Mischa Maisky, Emanuel Ax, Richard Goode, Alicia de Larrocha, Radu Lupu, Martha Argerich, Alfred Brendel, Horacio Gutierrez, Murray Perahia, Peter Serkin, Mitsuko Uchida, Tatiana Troyanos, Martin Fröst, Anne Akiko Meyers, Maureen Forrester, Frederica von Stade, Peter Schreier, Anne Sofie von Otter, Nobuyuki Tsujii, Dawn Upshaw, and Renée Fleming.

Orpheus has premiered works by Elliott Carter, Jacob Druckman, Mario Davidovsky, Michael Gandolfi, William Bolcom, Osvaldo Golijov, Fred Lerdahl, Gunther Schuller, Ellen Taaffe Zwilich, Susan Botti, David Rakowski, Bruce Adolphe, Peter Lieberson, Elizabeth Brown, Wayne Shorter, Brad Mehldau, and Shuying Li.

Their extensive catalog for Deutsche Grammophon includes Baroque masterworks of Handel, Corelli and Vivaldi, Haydn symphonies, Mozart symphonies and serenades, the complete Mozart wind concerti with Orpheus members as soloists, Romantic works by Dvořák, Grieg and Tchaikovsky and a number of twentieth-century classics by Bartók, Prokofiev, Fauré, Ravel, Schoenberg, and others.

Recent releases include a recording of English and American folk songs with countertenor Andreas Scholl (Decca); Creation, a collection of the Impressionist music from 1920s Paris with saxophonist Branford Marsalis (Sony Classical); a series of recordings of Mozart's greatest piano concerti with Richard Goode (Nonesuch); and a vigorous reading of The Four Seasons with Sarah Chang (EMI Classics).

Following the completion of The New Brandenburgs, Orpheus launched its Project 440 initiative that commissioned four emerging composers chosen by a diverse group of advisors through a nationwide selection process.