The largest island in the archipelago, boasting the best scenery, Santiago is also the most populated. Its residents are more African in culture, which is reflected in its musical traditions, markets and the many festivals held during the year.

Santiago is the site of Cape Verde's capital city, Praia, and the picturesque fishing town of Tarrafal. Praia has an interesting marine archaeology museum dedicated to documenting the various shipwrecks that have occurred around the islands. While not a popular tourist destination in its own right, Praia is the site of Cape Verde's busiest airport, and the walking around the city is a pleasant way to spend an hour or two before taking a ferry to the other islands.

The interior of Santiago is characterised by two towering chains of mountains, while the coastline sports small sandy palm-fringed coves. Other sites of interest on the islands include the historic old port city, Cidade Velha, was a major slave-trading post and retains cobbled lanes and stone buildings in the shadow of its old 15th-century fortress and Cathedral.