A significant portion of her career has been the performance of new music, including world premieres of operas, concert pieces, and songs composed for her by André Previn, Caroline Shaw, Kevin Puts, Anders Hillborg, Nico Muhly, Henri Dutilleux, Brad Mehldau, and Wayne Shorter.

"[6] Beyond opera, Fleming has sung and recorded lieder, chansons, jazz, musical theatre, and indie rock, and she has performed with a wide range of artists, including Luciano Pavarotti, Lou Reed, Wynton Marsalis, Paul Simon, Andrea Bocelli, Sting and John Prine.

She also sang for the 50th anniversary of the American Ballet Theatre in their production of Eliot Feld's Les Noces and returned to the New York City Opera to sing both the Countess in Le nozze di Figaro and Micaëla in Bizet's Carmen.

Also, there was Countess Almaviva in a landmark production of Le nozze di Figaro at the Met which also starred Cecilia Bartoli, Susanne Mentzer, Dwayne Croft, Danielle de Niese, and Bryn Terfel and which was broadcast on PBS' Great Performances.

She made her Carnegie Hall recital debut and sang Richard Strauss's Four Last Songs with Claudio Abbado and the Gustav Mahler Youth Orchestra at the Salzburg Festival.

Her singing can be found in the songs "The End of All Things", "Twilight and Shadow" and "The Return of the King" (Original Soundtrack) and "The Grace Of Undómiel", "Mount Doom", "The Eagles" and "The Fellowship Reunited" (The Complete Recordings).

[75] Massenet's Manon at the Met, Desdemona in Verdi's Otello at Covent Garden, and Thaïs in Vienna were part of her 2005 repertoire, in addition to concerts with the Berlin Philharmonic (Mahler's Symphony No.

Several recitals and concerts throughout the United States, Italy, Russia, Sweden and Austria took place, the latter being a celebration of Mozart's 250th Birthday with the Vienna Philharmonic which was broadcast live internationally.

On November 14, 2009, Fleming performed at a concert in Prague organized by Václav Havel to celebrate the 20th anniversary of the Czech Velvet Revolution, which also featured Lou Reed, Joan Baez and others.

[92] In the Spring of 2014, Fleming performed the role of Blanche Dubois in André Previn's operatic adaptation of A Streetcar Named Desire at Carnegie Hall in New York and later in Chicago and Los Angeles.

[102] During April and May 2019, Fleming appeared opposite actor Ben Whishaw in Norma Jeane Baker of Troy, the inaugural production in the Kenneth C. Griffin Theater at The Shed in Manhattan.

[103] On July 24, 2019, Fleming performed the world premiere of Penelope, a collaboration between Tom Stoppard and André Previn, with the Emerson String Quartet and pianist Simone Dinnerstein.

On September 25, 2020, Fleming appeared in a live concert with Vanessa Williams, titled "A Time to Sing", for a small, socially-distanced audience in the Kennedy Center Opera House.

[113] In November 2010, the Charlie Haden Quartet West released the jazz CD Sophisticated Ladies in which Fleming was a guest vocalist on the song "A Love Like This" by Ned Washington and Victor Young.

In 2015, Fleming sang "New York Tendaberry" accompanied by Chris Thile, Edgar Meyers and Yo-Yo Ma on the Billy Childs album Map to the Treasure: Reimagining Laura Nyro, the song winning the Grammy for Best Arrangement, Instruments and Vocals.

In 2017, Decca released Fleming's album Distant Light, which features four songs by the Icelandic composer Björk, Samuel Barber's Knoxville: Summer of 1915 and the Strand Settings, a four-song cycle composite by Anders Hillborg.

[119] On March 20, 2011, Fleming appeared in Grand Finale concert of the YouTube Symphony Orchestra with the Sydney Children's Choir, performing Mozart's "Caro bell'idol mio" K562, under the baton of Michael Tilson Thomas.

In November 2013, Fleming programmed and hosted a three-day festival held at the John F. Kennedy Center for the Performing Arts in Washington DC titled "American Voices", which explored the artistry and pedagogy of singing across musical genres.

[128] On November 9, 2014, with German Chancellor Angela Merkel and Mikhail Gorbachev in attendance, Fleming sang in a televised concert at the Brandenburg Gate to commemorate the 25th anniversary of the fall of the Berlin Wall.

[132] In the 2017 film Three Billboards Outside Ebbing, Missouri, Fleming's Decca recording of "The Last Rose of Summer" is heard in the opening scene and in the middle of the movie, which was nominated for Best Picture and Best Original Score.

[101] Fleming provided the singing voice of Roxann Coss, the American opera diva played by Julianne Moore, in the 2018 film Bel Canto, an adaptation of Ann Patchett's best-selling novel.

[137] On June 14, 2020, Fleming premiered a new work by composer John Corigliano, "And the People Stayed Home", a setting of Kitty O'Meara's poem, which was written in the first weeks of the pandemic and became a viral success on social media.

[139] Fleming was featured in the PBS Great Performances New Year's Eve telecast on December 31, 2020, in a concert taped at Mount Vernon that also included Joshua Bell, Denyce Graves, Jean-Yves Thibaudet, Yo-Yo Ma, Anna Deavere Smith, Audra McDonald, Brian Stokes Mitchell, and Patti LaBelle.

In September 2019, the NIH announced a commitment of $20 million to support research projects to explore the potential of music for treating a wide range of conditions resulting from neurological and other disorders.

Surgeon General Dr. Vivek Murthy, and later guests included author and neuroscientists Dr. Daniel Levitin, Director of the U.S. National Institutes of Health Dr. Francis Collins, Deepak Chopra, M.D., and Grateful Dead drummer Mickey Hart.

The goal of these conventions was to explore enhanced data collection for improved clinical trial design and, ultimately, to create a research toolkit to help develop music-based therapies for brain disorders of aging.

[149] On May 6, 2021, Fleming spoke in the Fifth International Vatican Conference (conducted online during the COVID-19 pandemic) on a panel exploring the therapeutic use of music for patients with heart failure and cardiovascular disease.

[152] Sing For Hope is a nonprofit that brings music programs and performances to under-resourced schools, healthcare facilities, refugee camps, transit hubs, and public spaces.

[153] On April 17, 2014, Fleming sang for the 25th anniversary concert of the Rainforest Foundation Fund at Carnegie Hall, performing solo and "Là ci darem la mano" in a duet with Sting.

[154] In 2015, Renée Fleming and Andrea Bocelli sang together for the first time ever at "Remembering Pavarotti", a benefit concert for pancreatic cancer research at the Los Angeles Music Center's Dorothy Chandler Pavilion on September 25.