In 1637, Strozzi founded his own academy, called Accademia degli Unisoni, where Barbara's talents as a singer and an instrumentalist and her beauty were important attractions. She was known for her intellect, learning, and wit, and presided over the meetings, naming the subjects to be debated during the evening. In 1638, the academy published an account of the meetings held by the group during the previous year, under the title Le Veglie de' Signori Unisoni. In it she is named, for the first time, as "Barbara Strozzi," the name under which she issued her publications.
At about this time her portrait was painted by a painter from Genoa named Bernardo Strozzi. A semi-nude showing her in dishabille, it depicts a very attractive young woman with dark chestnut hair and a challenging, even grave, and direct gaze. The original hangs in the Gemäldegalerie in Dresden under the title Female Musician with Viola da Gamba.
Barbara often wrote her music as the result of a challenge by members of the Academy to produce a work on a text they would give her. These were often love poetry with teasing, ironic lyrics. Her use of musical form is very flexible, adapting to the demands of the text, deftly moving between recitative, arioso, and aria in the longer works, such as the cantatas. In 1644, she issued the first of her eight publications, a volume of madrigals on Giulio Strozzi texts, dedicated to the Grand Duchess of Tuscany. She issued a second publication, of cantatas, ariettas, and duets, in 1651. The pace of her publication increased after 1652, when Giulio Strozzi died. The dedications in her further books of vocal music include various royalty, including Emperor Ferdinand II of Austria.
By 1651, she had four children. She never married. It is considered likely that the father of at least three of the children was Giovanni Paolo Vidman, a friend of Giulio. Her last published volume appeared in 1664. In 1665 she is known to have produced a group of songs for Carlo II, Duke of Mantua. Little is known of her life thereafter. The seven surviving volumes of her works (her Opus 4 is lost), containing several dozen works, some with string accompaniment, show her as one of the most accomplished song composers of her time.