Elisabetta was the first of four children of Margherita and Giovanni Andrea Sirani. Giovanni was an art merchant and painter of the School of Bologna, having been a favorite pupil of Guido Reni. He did not produce many works during his lifetime; instead, he took over Reni's job as a teacher, and became the master in the first life school.
Sirani first trained as a painter in her father's studio. There is evidence that Giovanni was not inclined at first to have his daughter as a pupil, but she picked up his technique nonetheless and became one of the most renowned painters in Bologna. An independent painter by 19, Sirani ran her family’s workshop. When her father became incapacitated by gout, she supported her parents, three siblings, and herself entirely through her art.
Elisabetta spent her life in Bologna, a city famous for its progressive attitude toward women’s rights. She became known for her ability to paint beautifully finished canvases so quickly that many visited her studio to watch her work. Her paintings were acquired by wealthy, noble, and even royal patrons, including the Grand Duke Cosimo III de Medici.
In addition to her substantial oeuvre, Sirani left an important legacy through her teaching. Her pupils included her two sisters, Barbara and Anna Maria, and more than a dozen other young women who became professional painters.