Villaume began his musical education at the Strasbourg Conservatory. He continued his studies in Paris at Khâgne and the Sorbonne where he studied literature, philosophy and musicology. At age 21, he became stage manager and dramaturg at the Opéra National du Rhin, where he met Spiros Argiris, who was then the music director of the Festival dei Due Mondi in Spoleto. Villaume subsequently studied conducting with Argiris, and later became an assistant conductor to Seiji Ozawa.
Villaume made his American conducting debut in 1990 with Le nozze di Figaro at the Spoleto Festival USA. He was named music director for opera and orchestra of the Spoleto Festival USA in October 2000, and held the post from 2001 to 2010. He made his Carnegie Hall debut in 2002 conducting the Montreal Symphony. He first conducted at the Metropolitan Opera in September 2004 in Madama Butterfly. Villaume first conducted at Dallas Opera in 1998. He made his debut with the Chicago Symphony Orchestra in 2007.In April 2013, Villaume was named music director of the Dallas Opera, with immediate effect. In November 2015, the Dallas Opera announced that Villaume's contract as music director had been extended through June 2022.
Internationally, Villaume made his Orchestre de Paris debut in 2000 as well as his debut at the Royal Opera House, Covent Garden conducting Les Contes d'Hoffmann in October 2000. In January 2007 he made his conducting debut at La Fenice in Venice with Meyerbeer's Il crociato in Egitto. He became chief conductor of the Slovenian Philharmonic Orchestra in 2008, and held the post through 2013. He became chief conductor of the Slovak Philharmonic in 2009, and held the post through 2016. In October 2014, the Prague Philharmonia announced the appointment of Villaume as its fourth chief conductor, effective with the 2015-2016 season, with an initial contract of 3 years.
- Maurice Emmanuel: Ouverture pour un conte gai / Symphony 1 & 2 / Suite française (Slovenian Philharmonic Orchestra; Conductor: Emmanuel Villaume). Timpani Recordings 1C1189.
- French Heroines (Nathalie Manfrino) Decca Records CD
- Puccini: La Rondine (Ainhoa Arteta and Marcus Haddock, Washington National Opera Orchestra and Chorus; Conductor: Emmanuel Villaume). Decca B001Q2RVTY DVD
- Souvenirs: (Anna Netrebko, Prague Philharmonica Orchestra). Deutsche Grammophon 4777451 CD
- Duets: (Anna Netrebko and Rolando Villazón) (Orchestras: Staatskapelle Dresden and Orchestre National de Belgique; Conductors: Nicola Luisotti and Emmanuel Villaume). Deutsche Grammophon 4776635 CD
- Massenet: Le Cid (Placido Domingo, Kennedy Center). House of Opera, 2005 DVD
- Massenet: Chérubin (Michelle Breedt, Patrizia Ciofi, Carmela Remigio,Giorgio Surjan, Teresa di Bari, Alessandra Palomba, Nicola Ebau, et al.; Orchestra and Chorus of Teatro Lirico di Cagliari; Conductor: Emmanuel Villaume) Dynamic CDS 508/1-2 CD and DV 33508 DVD
- Offenbach: La Grande-Duchesse de Gerolstein (Lucia Valentini-Terrani, Carlo Allemano, Thomas Morris, Richard Plaza; Orchestra Internazionale d'Italia; Conductor: Emmanuel Villaume) Dynamic CDS173 CD
- Meyerbeer: Il crociato in Egitto (Michael Maniaci, Patrizia Ciofi, Marco Vinco, Laura Polverelli, Fernando Portari, Iorio Zennaro, Silvia Pasini, Luca Favaron, Emanuele Pedrini; Orchestra and Chorus of Teatro La Fenice; Conductor: Emmanuel Villaume) Dynamic DV 33549 DVD
- Gian Carlo Menotti: Goya (Arthaus Musik DVD, 2011)
- Gustav Mahler: Symphony No.9 in D Major. Slovenska filharmonija, 2011
- Maurice Ravel: Daphnis et Chloé, NYOC, 2014
- Heroique: (Bryan Hymel, Prague Philharmonia). Warner Classics, 2015
- Echo Klassik Newcomer of the Year
- Bundesverband Musikindustrie Preis der deutschen Schallplattenkritik
- Académie Charles-Cros Grand Prix du Disque
- AllMusic Best of 2015
- Académie Charles-Cros Grand Prix du Disque
- Saint Saens, Ravel, Gershwin: concertos. (Andrew von Oeyen, Prague Philharmonia). Warner Classics, 2016
- Mark Adamo: Becoming Santa Claus. Dallas Opera DVD, 2017
- Giacomo Meyerbeer: Grand Opera (Diana Damrau, Orchestra and Chorus of the Lyon Opera). Warner Classics, 2017 Singer of the year Opus Klassik
- Eternamente: (Angela Gheorghiu, Prague Philharmonia). Erato, Warner Classics, 2017
- Maurice Ravel, Georges Bizet, Claude Debussy: Ma mère l'Oye, Symphony in C (Bizet), Fantaisie for piano and orchestra (Debussy). Prague Philharmonia. Warner Classics. 2018
- "French Conductor Named Music Director for Spoleto Festival U.S.A." New York Times. 2000-10-24. Retrieved 2007-12-19.
- William Furtwangler (2010-06-07). "A Lovely Adieu". The Post and Courier. Retrieved 2010-06-20.
- Jeremy Eichler (2004-09-24). "The Met's 'Madama Butterfly,' Revived but Not Reimagined". New York Times. Retrieved 2013-07-04.
- "The Dallas Opera Proudly Announces Our New Music Director Emmanuel Villaume" (Press release). Dallas Opera. 30 April 2013. Retrieved 2013-07-04.
- Scott Cantrell (2013-04-30). "Dallas Opera names Emmanuel Villaume new music director". Dallas Morning News. Retrieved 2013-07-04.
- "Villaume novi šef dirigent, Pehlivanian odhaja". Delo. 2008-06-05. Retrieved 2013-07-04.
- Boštjan Tadel (2013-05-06). "Emmanuel Villaume, dirigent: V Sloveniji je Preobilje Kulture". Pogledi. Retrieved 2013-07-04.
- Raymond Johnston (2014-10-22). "PKF - Prague Philharmonia names new conductor". Prague Post. Archived from the original on 2015-09-27. Retrieved 2015-09-08.
- "University growth splits commencement ceremonies in two" (PDF). Portico. Summer: 17. 2003. Retrieved 2013-07-04.
- Echo Klassik (24 August 2015). "Echo Klassik 2015: This year's prize-winners have been chosen."
- Neue Musikzeitung (14 August 2015). "Preis der Deutschen Schallplattenkritik: die Bestenliste 3/2015 ist erschienen"
- AllMusic (2015). Year in Review
| Music Director, Spoleto Festival USA
| Chief Conductor, Slovenian Philharmonic Orchestra
| Chief Conductor, Slovak Philharmonic
| Music Director, Dallas Opera
| Chief Conductor, Prague Philharmonia