Construction of the autovía began in 1992 when the section between Antequera and Málaga was built as an upgrade of the N-331. This was renumbered A-45 in 2003, as part of the general renumbering of Spanish autovías. The section between Córdoba and Benamejí was built in the mid-2000s, running parallel to the N-331, and the section between Benamejí and Antequera was built in 2009.
The section between Puerto de Las Pedrizas, several kilometres south of Antequera, and Málaga is frequently used by drivers travelling to and from Córdoba, Seville (via the Autovía A-92) and Granada (via the Autovía A-92M and A-92). In the late 2000s and early 2010s, the Autopista AP-46 was built to alleviate the traffic on this section.