Yannick has worked with many leading European ensembles and enjoys close collaborations with Berliner Philharmoniker, Wiener Philharmoniker, Bayerischer Rundfunk Sinfonieorchester and Chamber Orchestra of Europe; between 2008 and 2014, he was also Principal Guest Conductor of London Philharmonic Orchestra. He has appeared many times at the BBC Proms and at many European festivals, among them Edinburgh, Lucerne, Salzburg and Grafenegg (Vienna). North American summer appearances include New York's Mostly Mozart Festival, Lanaudiere, Vail and Saratoga along with Domaine Forget Festival in Charlevoix. With the Philadelphia Orchestra, he goes regularly to Carnegie Hall where he has been Perspectives Artist in 2019-2020. He also conducts master classes, notably at two of the most renowned institutions, the Curtis Institute of Philadelphia and the Julliard School of New York. In Quebec, he directs an academy of young conductors linked to the Orchestre Métropolitain, in close collaboration with the Domaine Forget Summer Festival.

A long-term collaboration with the Baden Baden Summer Festival, La Capitale d'été, resulted over the years in several concerts and recordings of operas with the Chamber Orchestra of Europe (see next paragraph), as well as the complete symphonies by Beethoven (Summer 2021) and the Brahms cycle (Summers 2022 and 2023). 

He regularly conducts the Philadelphia and Rotterdam Orchestras as well as the Chamber Orchestra of Europe on Asian or European tours; in November 2017, he conducted the Orchester Métropolitain de Montréal on its very first European tour, which was a huge success, followed, in November 2019, by a very prestigious American tour with singer Joyce DiDonato; a second American tour is planned with the Orchestre Métropolitain which will take them to Carnegie Hall in March 2024. During Summer 2023, he conducted a very successful European Tour with the MET Orchestra who had not travelled since many years; an Asian Tour is planned. 

Yannick is as comfortable at the opera as at the concert. After having cut his teeth at the Opéra de Montréal from 2000 to 2004 in L'Incoronazione di Poppea, The Barber of Seville, Cosi fan tutte, Pelléas et Mélisande and L'Elisir d' amore, he returns sporadically for Wozzeck, Madame Butterfly, Salomé and Elektra. He made his debut at the Salzburg Festival in 2008 with a new production of Romeo and Juliet by Gounod and returned there in 2010 and 2011 for Don Giovanni by Mozart. It was during the 2009-2010 season that he made his debut at the Metropolitan Opera (MET) in a new production of Carmen by Bizet; thereafter, he returned there each season to conduct Don Carlo, Faust, La Traviata, Rusalka, Otello, Der Fliegende Hollander, Parsifal and Elektra before becoming its musical director; in this position, he conducted La Traviata, Pelléas et Mélisande, Dialogues des Carmélites, Turandot, Wozzeck, Tosca, Fire shut up in my bones, Eurydice and Don Carlo (in French). In addition, during the 2022-2023 season, he will in turn conduct The Hours, Lohengrin, Champion and La Bohême. During the season 2023-2024, he'll conduct Dead Man Walking, Florencia in el Amazonas, La Forza del Destino and Roméo et Juliette

He has conducted at the Teatro alla Scala (Milan), the Royal Opera House (Covent Garden, London), the Netherlands Opera (Amsterdam) and the Vienna Staatsoper (Vienna). With the Rotterdams Philharmonisch Orkest, just before the start of the pandemic, he conducted a semi-staged version of Die fraù ohne schatten by Richard Strauss. In 2011, he undertook the cycle of Mozart's last operas for the Festspielhaus Baden Baden, all recorded "live" by Deutsche Grammophon; to date, the following titles have appeared: Di Zauberflöte; La Clemenza di Tito; Le Nozze di Figaro; Entführung aus dem Serail; Cosi fan tutte; Don Giovanni, most of them with the Chamber Orchestra of Europe. In April 2022, with the Rotterdams Philharmonisc Orkest, he conducted Rheingold by Richard Wagner in concert version during a tour in Rotterdam, Paris, Dortmund and Baden Baden which drew the highest praise to the entire production. A similar tour is planned with Walküre by Richard Wagner in March 2024. 

Several films or sequences have been shot on Yannick Nézet-Séguin's career, the most complete, released in 2021, entitled Yannick, an Artist's Journey by Susan Froamke, produced by the MET. In addition, Yannick has participated as a Conducting Consultant in 2022 and 2023 in the production of two films: Maestro, an American film by Bradley Cooper (who also plays the title role), also starring Carrie Mulligan, chronicling the life of Leonard Bernstein (on Netflix in November 2024); and Happy Days, a Quebec film by Chloé Robichaud starring Sophie Desmarais in the role of a young Conductor. 

The maestro records exclusively for Deutsche Grammophon. September 2013 marks his first symphonic recording under this prestigious banner; for the occasion, he directs the Philadelphia orchestra which had not recorded under a renowned label since 1997; their record Stravinsky (The Rite of Spring)-Stokowski (transcriptions by Bach and Stravinsky) proved to be a huge success. With the Chamber of Europe Orchestra, he recorded the complete Mendelssohn Symphonies as well as the complete works of Schumann Symphonies; with the Rotterdams Philhamonisch Orkest, a souvenir box; with Daniil Trifonov and the Philadelphia Orchestra, two discs of 4 piano concertos by Rachmaninoff. His DG discography includes several other recordings, including Tchaikovsky with Lisa Batiashvili and the Rotterdam Philharmonic Orchestra; and Visions of Prokofiev with Lisa Batiashvili and the Chamber Orchestra of Europe. Following a few stage performances of Mass by Leonard Bernstein, Yannick conducts the Philadelphia Orchestra as well as all the participants in a recording which was released in March 2018. In 2021, still with the Philadelphia Orchestra, he engraves Florence Price's Symphonies 1 and 3; this disc earned him a Grammy award for "best orchestral performance". With the same orchestra, he recorded the album Price-Dawson, nominated for the 2024 Grammys. 

With ATMA Classique and the Orchester Métropolitain de Montréal, with whom he began recording in 2000, a special box set brings together all the Bruckner Symphonies recorded over the years. Thereafter, he undertook with them the Cycle Sibelius whose latest album will be released in 2024. A return to the piano during the pandemic allows his first solo piano album, Introspection, to see the light of day on Deutsche Grammophon (February 2021). Other recordings are available on various labels: Rotterdam Philharmonic Orchestra (EMI Classics, BIS); London Philharmonic Orchestra (LPO label); Montreal Metropolitan Orchestra (ATMA Classic); Berliner Philharmoniker (house label); Wiener Philharmoniker (Sony Classical); etc