Born in a musical family, Karine Deshayes studied musicology at the Sorbonne and learnt singing at the Conservatoire de Paris. Mireille Alcantara was her teacher. She had also received advice from Régine Crespin.
In 1998, she joined the troupe of the Opéra de Lyon. The opera houses of the region (Avignon, Bordeaux, Toulouse...) regularly invited her.
Her career took off quickly. Karine Deshayes made her debut at the Opéra de Paris in 2002 (in Rusalka's Marmiton, by Dvorak), at the 2005 Salzburg Festival (Second Lady of Mozart's The Magic Flute, under the baton of Riccardo Muti), at Metropolitan Opera of New York in 2006 (Siebel of Gounod Faust).
Karine Deshayes has been named twice (2011, 2016) 'Lyric Artist of the Year' by the Victoires de la Musique Awards.