Born in 1980, Spyres is a native of the small town of Mansfield, Missouri, in the Ozark Mountains in the southern part of the state. Both of his parents were music teachers. His entire family was musical, and he was named after an uncle who had hoped to become an opera singer, but died of throat cancer before he could do so. Spyres grew up singing regularly at weddings and funerals, and he gained early experience on the operatic stage, appearing for the first time at the nearby Springfield Regional Opera when he was 18. Local opera helped launch Spyres' career: by the time he was 22, he had appeared in six full-scale operatic productions, many more than other voice students he met around that time. When Spyres was 24, he moved to Austria and studied at the Vienna Conservatory (now the Private University of Music and Art of the City of Vienna).
Spyres made his debut at the Teatro San Carlo in Naples in 2006, playing Jaquino in Beethoven's Fidelio. He then appeared as Alberto in Rossini's La gazzetta at the Rossini in Wildbad festival in Germany, and went to Japan as part of a touring production of La traviata. Invited back to Bad Wildbad, he scored a breakthrough in the title role of Rossini's Otello in 2008. Since then, Spyres has appeared in major opera houses, including La Scala and Covent Garden, under the likes of Riccardo Muti, Sir John Eliot Gardiner, Valery Gergiev, and Emmanuelle Haïm. Spyres returned to his hometown as artistic director of the Springfield Regional Opera in 2016. In 2020, Spyres made his debut at the Metropolitan Opera in New York as Faust in Berlioz's La damnation de Faust.
In addition to appearing on recordings of operas by Donizetti, Rossini, Berlioz, and Giovanni Simone Mayr, Spyres has released the recital albums A Fool for Love (2011) and Espoir (2017). The latter explored the repertoire of 19th century tenor Gilbert Duprez, who sang both French and Italian opera. In 2019, he was heard as tenor soloist on a Philharmonia Orchestra recording of the Berlioz Requiem, Op. 5, conducted by John Nelson. He returned the following year with Rossini: Amici e Rivali, a collection of Rossini duets for two tenors on which he teamed with Lawrence Brownlee. ~ James Manheim, Rovi