He was born at Urbino, an inherited the title of count of Cantiano after the death of his brother Buonconte in 1458.
In 1464 he abandoned the studies for the military career, following his father against the papal army led by Alessandro Sforza.
The two were both at the service of Alfonso V of Aragon in the Kingdom of Naples in 1474.
His wife was Emilia di Carpi, the daughter of count Marco II of Carpi and Sassuolo; she was perhaps portrayed by Raphael in 1504-1505.
Antonio da Montefeltro died at Gubbio in 1508, likely of syphilis.