His real name was Domenico Bigordi. He was said to have been a pupil of Baldovinetti. As well as working in Florence he was also in Rome, San Gimignano and Pisa.
He ran an active studio and was partnered by his brother David. They specialised in extensive fresco cycles, such as those in Sta Maria Novella and Santa Trinita in Florence. The young Michelangelo was an apprentice with Ghirlandaio, whose son Ridolfo also became a painter.