The island measures 35 km north-south and up to 9.5 km east-west, with a total area of 253.8 km² (98 square miles). It features a chain of high volcanic mountain ridges which rises to a height of 1298 meters (4257 feet) at its northern end (Mount Augusta).

Guadalupe shares the California chaparral and woodlands ecoregion with the Channel Islands of California in the United States, but the island has been practically denuded of all plants higher than a few centimeters due to tens of thousands of goats.

Originally brought there in the early 19th century by primarily Russian whalers and sealers for provisions when stopping over, the population eventually eliminated most vegetation; the number of goats declined to a few thousand. Eradication of the goats was long envisioned, but logistical difficulties such as island size and lack of suitable spots for landing and encamping hunters and material prevented this.