Simona Molinari was born in Naples on February 23, 1983, and grew up in L'Aquila. She started singing lessons at eight, worked first in light music and jazz, then studied classical singing and took her diploma at the Alfredo Casella conservatory in L'Aquila. Her early working years were spent in Italian piano bars. In 2006 she won the best singer prize at the Premio 25 Aprile, and in 2007 she began a jazz-pop project with the producer Carlo Avarello, who later produced Croce e delizia, Tua and Dr. Jekyll Mr. Hyde. The same year she made her theatre debut and sang in the Italian production of the musical Jekyll & Hyde alongside Giò Di Tonno.

She won the Sanremolab competition in December 2008, which sent her to the Sanremo Festival in 2009 with "Egocentrica." On the third evening she sang it as a duet with Ornella Vanoni, and the album Egocentrica followed on February 20, 2009. It mixes originals with standards ("La Vie en Rose," "Que Sera, Sera," "Nel blu dipinto di blu") and won the Premio Lunezia in the New Stars category that July. Later in 2009 she recorded Brahms's lullaby with the pianist Nazzareno Carusi for a charity single after the L'Aquila earthquake, and sang at the Amiche per l'Abruzzo benefit concert at San Siro on June 21.

Croce e delizia (June 22, 2010) is the record where the jazz side is plainest. Fabrizio Bosso and the Solis String Quartet are among the guests, it includes a live reading of Jobim's "How Insensitive" recorded in Hong Kong, and "Amore a prima vista," her duet with Vanoni, reached No. 10 on the Italian singles chart and won her a second Premio Lunezia, this time in the Jazz d'Autore category. A Wind Music Award for best young talent followed in 2010. Between 2010 and 2011 she toured Asia, Europe, Montreal and Rio de Janeiro, a run that included the Blue Note in Tokyo.

Tua (October 18, 2011) added "Forse," a duet with the Hong Kong jazz musician Danny Diaz, and "In cerca di te," a reworking of "Perduto amore" with Peter Cincotti; Dado Moroni is credited for an arrangement collaboration on the closing track. Dr. Jekyll Mr. Hyde (February 14, 2013) leans furthest toward jazz and Brazil. Cincotti plays piano on four tracks, Roberto Gatto drums on two, and Gilberto Gil plays guitar on "Sampa Milano," which the two singers also issued as a promotional single in 2012. The title song is a posthumous piece by Lelio Luttazzi and Alberto Zeppieri, and Luttazzi's own piano is heard on another track. The album reached No. 16 on the Italian chart. She returned to Sanremo in 2013 with Cincotti, singing "La felicità," which finished 13th and went gold, and she played the Blue Note in New York that December.

Her Warner years ended after the birth of her daughter in 2015, which she has described as the reason her contract was not continued. Casa mia (December 4, 2015) debuted at No. 28 in Italy. She toured a tribute to Ella Fitzgerald, Loving Ella, in 2015 and 2017, and was a guest at Umbria Jazz in 2017. In 2019 she took the lead role in Walter Veltroni's film C'è tempo, and in 2020 she returned to Sanremo as the duet partner of Raphael Gualazzi, with whom she sang "E se domani" and recorded it on his album Ho un piano.

Petali (April 1, 2022, BMG) brought her first Targa Tenco for best interpreter. Her second came in 2024 for Hasta siempre Mercedes, a tribute to the Argentine singer Mercedes Sosa that grew out of the stage piece El Pelusa y la Negra, an imagined conversation between Sosa and Diego Maradona. Claudio Filippini plays piano and co-produced, Paolo Fresu plays trumpet on "Canción de las simples cosas," and Tosca sings with her on "Mon Amour." In 2024 she also received a Callas Tribute Prize in New York. Since 2024 she has released swing and electro swing singles with the producers Pisk and Papik, and from 2025 she has toured the stage show La donna è mobile.

Molinari is a pop-chart and Sanremo artist whose records are consistently built from jazz materials: swing and bossa nova rhythm sections, standards, a bright, light mezzo voice, and arrangements by jazz-trained players. Most of her public profile in Italy comes from the festival and the singles chart, and the two Targa Tenco prizes are awards for singer-songwriter interpretation rather than jazz awards. The jazz recognition is the Premio Lunezia in the Jazz d'Autore category (2010), the guest slot at Umbria Jazz in 2017, and the jazz musicians who keep appearing on her records: Bosso, Moroni, Gatto, Cincotti and Fresu.

Her models are the Italian swing tradition around Lelio Luttazzi, whose last song she recorded, and the American vocal standards she sings on Loving Ella. The Sosa tribute is Latin American song repertoire arranged for guitar, strings and piano, and it is stated plainly here that it is not a jazz record, although Fresu's trumpet and Filippini's piano give it a jazz-side voice.