He is the music director of the Orchestre Métropolitain (Montréal), the Metropolitan Opera (New York City), and the Philadelphia Orchestra.

In 1995, he founded his own professional orchestral and vocal ensemble, La Chapelle de Montréal, with whom he performed two to four concerts a year until 2002.

[4] Nézet-Séguin became music director of the Orchestre Métropolitain (Montréal) in 2000, and principal guest conductor of the Victoria Symphony (British Columbia, Canada) in 2003.

In December 2006, the RPhO announced the appointment of Nézet-Séguin as their 11th Principal Conductor, by a unanimous vote, starting with the 2008–09 concert season,[10] with an initial contract of 4 years.

[22][23] Nézet-Séguin began annual appearances with the Metropolitan Opera in New York City in 2009, making his début on 31 December 2009, conducting a new production of Carmen.

On 2 June 2016, the Metropolitan Opera announced the appointment of Nézet-Séguin as the next music director, effective with the 2020–2021 season, with an initial contract of four years.

In February 2018, the company announced Nézet-Séguin's rescheduled assumption of the title of music director two years early, as of the 2018–2019 season,[30] following the Met's dismissal of James Levine for sexual misconduct.

On 14 March 2022, Nézet-Séguin and the Metropolitan Opera performed a charity concert for Ukraine in the wake of the Russian invasion of the country with all ticket and album sales and donations supporting war relief efforts,[31] a concert recorded for a digital release album on the Decca Classics and Deutsche Grammophon labels.

He served as a creative consultant on Days of Happiness (Les Jours heureux), a 2023 drama film by Chloé Robichaud about an orchestra conductor.