Georges Mathias studied piano under Kalkbrenner and Chopin in his youth. For Chopin, who generally did not teach children, this was an exception, alongside the short-lived Carl Filtsch. Clara Wieck, who went on a concert tour to Paris in 1839, was scheduled to give lessons to Mathias there. However, upon hearing his performance, Clara was so astonished by his perfected playing that she spent time playing duets with him instead of giving lessons. His prodigy status can be inferred from a letter Clara sent to her father, Friedrich Wieck, in which she described Mathias as "a second Liszt" and stated that "he needs no teacher." The following year, Mathias debuted playing Beethoven's Piano Trio "Archduke" Op. 97 and Weber's "Konzertstück" Op. 79. At this time, Jean-Delphin Alard (1815–1888), who played the violin in the "Archduke," and Auguste-Joseph Franchomme (1808–1884), who played the cello, had also formed a trio with Chopin. Furthermore, Alard and Franchomme later performed in trios with Alkan and Francis Planté (1839–1934).

Among Mathias's particularly significant achievements as a pianist is his performance of the first piano part in the premiere of Rossini's "Petite messe solennelle" (original version with accompaniment by two pianos and harmonium) on March 14, 1864.

Mathias served as a professor at the Paris Conservatoire from 1862 to 1887, during which time he trained many pupils. For this reason, he is considered as important as Carl Mikuli (1821–1897) in transmitting Chopin's tradition to later generations. Consequently, the recordings of Chopin's works performed by one of his pupils, Raoul Pugno (1852–1914), are highly regarded not only for their high quality but also as one of the means by which authentic Chopin performance has been conveyed to the present day. Other important pianists who studied under Mathias include Isidore Philipp (1863–1958), who also became a renowned professor at the Paris Conservatoire; Teresa Carreño (1853–1917), who had studied under Gottschalk in her youth; and Ernest Schelling (1876–1939), who later also studied under Paderewski. Furthermore, Dukas and Satie also studied piano with Mathias.

After debuting as a pianist, Mathias entered the composition department of the Paris Conservatoire in 1842, studying under Henri Montan Berton (1767–1844) and Jacques-Fromental Halévy (1799–1862), known for his opera "La Juive." Consequently, Mathias's compositions, unusually for a pupil of Chopin, include symphonies and sacred music, though most are piano pieces (he also wrote piano trios and songs). Among his works are sonatas and etude collections, as well as "Caprice-Polka" Op. 40, dedicated to Burgmüller (a virtuosic piece whose difficulty would be unimaginable from the dedicatee's name), and "Allegro Symphonique," which Cortot and Ravel played in their Paris Conservatoire examinations (sometimes mentioned in Ravel's biographies as a piece he played for an exam).