Santa Fe Island was formed by lava flows that emerged under the sea and were subsequently uplifted (although recent evidence suggests later subaerial activity). The island, 24 square kilometers, is crossed by a series of parallel reefs formed by fault activity. This island has lava that is 3.9 million years old, making it the oldest island in the archipelago. Santa Fe offers one of the most beautiful and protected bays of the islands. Its turquoise lagoon is protected by a peninsula of islets that form an ideal anchorage.

A wet landing on a white sand beach brings visitors in contact with one of the many sea lion colonies. Males fight for the right to own the beach, while smaller males pose as females to indirectly mate. Galapagos hawks are often easy to approach, high in the salt bushes, and an uphill trail leads to the cliffs, where dense thickets remain on the inland side. The cliff edge offers an expansive view of the ocean. The giant cactus lives up to its name with its tree trunks. Beneath the cacti, some of which are subspecies endemic to the island, are endemic species of land iguanas waiting in the shade of falling flowers or fruit to become a delicious part of their diet.