Major ports along this stretch of coastline included Veracruz, Porto Bello, Cartagena de Indias and Maracaibo.

The Spanish Main then encompassed the Caribbean coastline from the Isthmus of Darien in Panama to the Orinoco delta on the coast of Venezuela.

[citation needed] From the 16th to the early 19th century, enormous wealth was shipped from the Spanish Main to Spain in the form of gold, silver, gemstones, spices, hardwoods, hides and other valuable goods.

Other goods originated in the Far East, having been carried to the Pacific coast of Spain's possessions on the Manila galleons, often through the port of Acapulco, then transported overland to the Spanish Main for onward shipment to Europe.

The Spanish Main became a frequent target for pirates, buccaneers, privateers and countries at war with Spain, seeking to capture some of these riches.