In 1608 she began collaborating with the poet Michelangelo Buonarroti the younger in writing works for court entertainment. She wrote an opera called Il ballo delle zigane for Carnival season in 1615. In 1616 Cardinal Carlo de' Medici made an official trip to Rome and took her and her husband, Giovanni Battista Signorini Malaspina, along. She was so well-received by the Roman dignitaries that she was granted leave to undertake a concert tour of northern Italy. It was highly successful and earned her great acclaim. In return, she wrote a book of songs the next year and dedicated it to the Cardinal. She started taking on students, and continued to sing regularly at court for several more years. In 1625 she wrote an opera to commemorate the visit to Florence of the future king of Poland. This opera, La liberazione di Ruggiero dall'isola d'Alcina, became her most popular work. In 1682 it was given in Warsaw, making it the first Italian opera to be played in that country. Her husband died in 1627. She continued to sing on a few occasions, but her name disappears from official records soon afterwards, suggesting she retired. In 1640 there is a death notice for a Francesca Caccini, listed as the wife of a senator. It is likely that this is she, suggesting that when she remarried she withdrew from professional music-making.
Her collection of vocal music, Il primo libro delle musiche (1618), is one of the finest collections of early solo songs. It follows the monodic style developed by her father and includes pieces in various genres, including madrigals, canzonettas, and several others. The vocal writing is among the most brilliant of the early Baroque era. She wrote out many of the ornamentations and trills. The melodic lines have a strong, arching character, and other inventive features, all adding up to a strong dramatic presentation of the texts.