Ana Popovi?'s father first introduced her to the blues, through an extensive record collection and sessions hosted at the family home. Popovi? founded her first band at age nineteen. Within a year, she was playing outside of her home county Yugoslavia and opening shows for American blues musicians such as Junior Wells. Her band, Hush, released the album Hometown in 1998. The next year, Popovi? relocated to Amsterdam, Netherlands, to study jazz and world guitar at the Conservatory.[1] In 2000, Popovi? formed the 'Ana Popovic Band' that became a fixture on the Dutch blues scene, and ventured into neighboring Germany. Popovi? signed with the German based Ruf Records, and released three albums; Hush! (2001), Comfort to the Soul (2003) and Ana! (2005: live CD & DVD).

In 2003, Popovi? was nominated for a W. C. Handy Award in the United States.
In 2006, Popovi? signed a recording contract with the Los Angeles, California, based EclectoGroove Records (a division of Delta Groove Music.) For EclectoGroove she recorded a further three albums: Still Making History (2007), Blind For Love (2009) and Unconditional (2011). Both Still Making History and Unconditional reached number one in the United States Billboard Blues Chart.