Ponchielli's parents were poor shopkeepers in whose backrooms he was born August 31, 1834. Giovanni Ponchielli and Caterina Mora were engaged as tabacchi, a type of small business found in Italy today. Paderno Fasolaro was a small agricultural hamlet located about six miles from the provincial capitol, Cremona. Amilcare's musical talent appeared very early and a local count, Giovanni Battista Jacini, provided a scholarship to the Milan Conservatory for him in 1843 where his main teachers were Felice Frase and Alberto Mazzucato. While at the conservatory he composed a wide range of musical genre among which the instrumental work Scena campestre was particularly notable. Upon his graduation in 1854, Ponchielli located to Cremona where he became active in its musical life and enjoyed the support of the composer Ruggero Manna who was organist in the cathedral and conductor in the local theater. To make ends meet Ponchielli served as an organist and as a conductor in various opera houses throughout northern Italy. His twelve-year career as a bandmaster developed from this same need.

Ponchielli's compositional endeavors were not confined to the band medium during this period, however. As early as 1856 he presented his opera Promessi sposi (based on Alessandro Manzoni's novel) in the Teatro concordia in Cremona. Two operas, La Savoiarda (1860) and Roderigo re dei Goti (1863), enjoyed some success. In 1868 Ponchielli won a competition for a position in counterpoint and fugue at the Milan Conservatory; however, he lost out when the search committee appointed Franco Faccio instead. Ponchielli's success was assured in 1872 when a second version of Promessi sposi was performed at the Teatro Dal Verme in Milan. The prima donna was Teresa Brambilla who would marry Ponchielli in 1874.

Sometime during 1872-73 Ponchielli moved to Milan where he was engaged by Giulio Ricordi who had taken over from Fernando Lucca with whom Ponchielli had published several early works. This relationship was fraught with problems and may have been a reason for the unevenness of some of Ponchielli's later works. 1873 was an infertile year while the ballet Le due gemelle was performed at La Scala in 1874. Ricordi commissioned two works for the funeral of Manzoni, but those have been lost. A funeral march for band, Per i funerali di Manzoni, (and produced for various piano combinations) does survive. A comic chamber opera Il parlatore eterno was staged in Lecco that same year. The "grand" Italian opera I Lituani was also officially debuted at La Scala. It was re-done and revived in 1875 and was performed in St. Petersburg in 1885 as Aldona. An ascendant Lithuania was not a popular topic in Russia at that time.

Ponchiell's greatest success arrived in 1876 with the premier at La Scala of La Gioconda. With a libretto by Arrigo Boito(writing under the pseudonym "Tobia Gorrio") Ponchielli was hailed as the successor to the aged Giuseppe Verdi. The final version did not arrive until a performance in Genoa in 1879. Other libretti were set around this time, but no final works ever appeared in Ponchielli's lifetime.

As a conductor, Ponchielli was involved with performances of works by Massenet and Wagner as well as Italian composers. His opera Il figlio prodigo was produced at La Scala in 1879 with few later performances. Ponchielli's last years were devoted to two positions: professor at the Milan Conservatory and Maestro di capella at St. Mary Major in Bergamo (after 1882). Among his students in Milan were Giacomo Puccini (1858-1924), Pietro Mascagni (1863-1945), and musicologist, Giovanni Tebaldini (1864-1952). A curious inversion occurs when, upon hearing a late work by Ponchielli, many are moved to compare it to the better-known works by Puccini. A tepid reception greeted his last opera Marion Delorme upon its premier at La Scala in 1885.

On January 8, 1886 Ponchielli was brought home from the conservatory by his students, too fatigued to teach, thanks to a respiratory infection. His death followed on January 16, 1886. In the aftermath of his death, the theater in Cremona was renamed Teatro Ponchielli, Paderno Fasolaro became Paderno Ponchielli, and a statueof a mature Ponchielli was commissioned that now resides in the Piazza Roma.