- Santa Cruz (Argentina) - a province in the Patagonia (Argentina) region
- Santa Cruz (department, Bolivia) - Bolivia's largest department
- Santa Cruz (city, Bolivia) - capital city of Santa Cruz (department, Bolivia)
- Santa Cruz (Galapagos) (Isla Santa Cruz, or Indefatigable Island) - one of the Galapagos Islands
- Santa Cruz (Laguna)
- Santa Cruz (Manila) - A district of Manila.
- Santa Cruz (Marinduque)
- Santa Cruz (Madeira) - a city on Madeira Island, in the Madeira archipelago
- Santa Cruz Islands - an archipelago forming part of the Solomon Islands
- Santa Cruz de Tenerife - capital city of the island of Tenerife, and joint capital (with Las Palmas de Gran Canaria) of the Canary Islands
- Santa Cruz (California) - a city in Santa Cruz County, in the Bay Area region of California
- Santa Cruz County (Arizona) - in South Central Arizona
- Santa Cruz County (California) - in the Bay Area region of California
- Santa Cruz Island - the largest of the five islands that make up the Channel Islands National Park, in Southern California
- Santa Cruz Mountains - a mountain range in central California
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