Biss started learning the piano at age six, studying with Karen Taylor and Evelyne Brancart at Indiana University Bloomington's Jacobs School of Music, where both his parents taught violin.

He took a very healthy road that started with chamber music, both with his mother and then more extensively at places like Ravinia and Marlboro, and he got to be known by the elders in the profession as somebody to look out for.

[9] His European career was launched in 2002 when he became the first American to be selected as a BBC New Generation Artist,[10] winning a Borletti-Buitoni Trust Award the following year.

[26] An enthusiastic performer of chamber music, Biss has appeared with renowned artists such as Uchida,[27] Fleisher, Richard Goode,[28] Midori,[29] and Kim Kashkashian.

[30] In 2010, Biss was appointed to the piano faculty as Neubauer Family Chair at his alma mater, the Curtis Institute of Music.

[43] Biss premiered "The Blind Banister" by Timo Andres, which was named a finalist for the Pulitzer Prize for Music, "City Stanzas" by Sally Beamish, Il sogno di Stradella by Salvatore Sciarrino, "Watermark" by Caroline Shaw, and Gneixendorfer Musik - eine Winterreise by Brett Dean.

Biss has begun examining, both in concert and academically, the concept of a composer's "late style", focusing on musicians who went in surprising directions at the ends of their lives.

He has put together several programs of Bach, Beethoven, Brahms, Britten, Elgar, Gesualdo, Kurtág, Mozart, Schubert, and Schumann's later works, which he performed with the Brentano Quartet and Mark Padmore in the UK, Italy, the Netherlands, and across the United States.

He also gave masterclasses at Carnegie Hall in connection with the idea of late style and published Coda, a Kindle single on the topic, in 2017.

This included the complete sonatas at the Wigmore Hall and Berkeley, multi-concert-series in Washington, Philadelphia and Seattle, and recitals in Rome, Budapest, New York and Sydney.