Villa de San Antonio is a municipality in the Honduran department of Comayagua.

The municipality consists of a casco urbano (main town), with approximately 7,000 residents, and a large number of 'aldeas' or villages, which bring the municipality's entire population to 17,000.

Principal economic activities include farming, factory work, and construction.

There are two orphanages within the 'casco urbano;' the independent Hogar Tierra Santa and the Hogar San Antonio, affiliated with the Catholic charity Apufran.

The municipality of Villa de San Antonio was founded in 1537, the same year as the nearby city of Comayagua.