"Bienvenidos a la ciudad imperial del Cusco," announces the flight attendant when your plane touches down at a lofty 3,300 meters (10,825 feet) above sea level. "Welcome to the imperial city of Cusco." This greeting hints at what you're in for in Cusco, one of the world's great travel destinations.

The juxtaposition of cultures—Inca and Spanish colonial, but also modern—makes this city fascinating. This is a rare place where, if you take the time to sit and observe, you will see a culture that is going through a transformation in front of your very eyes. Where else can you see a child in traditional dress leading a llama on colonial streets while talking on a smartphone?

The area's rich history springs forth from the Inca tale that describes how Manco Cápac and his sister-consort Mama Ocllo were sent by the Sun God, their father, to enlighten the people of Peru. Setting off from Lake Titicaca sometime in the 12th century with the directive to settle only where their golden staff could be plunged fully into the soil, they traveled far across the altiplano (high plains) until reaching the fertile soils surrounding present-day Cusco. They envisioned Qosqo (Cusco) in the shape of a puma, the animal representation of the Earth in the indigenous cosmos, which you can still see today on city maps. But not all was Inca in southern Peru. Not far from Cusco sits Pikillacta, a pre-Inca city constructed by the Wari culture that thrived between AD 600 and 1000. It's an indication that this territory, like most of Peru, was the site of sophisticated civilizations long before the Inca appeared.

By the time Francisco Pizarro and the Spanish conquistadors arrived in 1532, the Inca Empire had spread from modern-day Ecuador in the north down through Peru and Bolivia to Chile. Sadly, the city's grandeur could do little to save an empire weakened by internal strife and civil war. Stocked with guns and horses, which the Inca had never seen, and carrying new diseases, against which they had no immunity, the Spanish arrived with the upper hand, despite smaller numbers. In 1532, the Spanish seized Atahualpa, the recently instated Inca ruler, while he was in Cajamarca to subdue rebellious forces. The Inca's crumbling house of cards came tumbling down, though pockets of resistance remained for years in places such as Ollantaytambo.

After sacking the Inca Empire, Spanish colonists instituted new political and religious systems, superimposing their beliefs onto the old society and its structures. They looted gold, silver, and stone and built their own churches, monasteries, convents, and palaces directly onto the foundations of the Inca sites. This is one of the most striking aspects of the city today. The Santo Domingo church was built on top of Qorikancha, the Temple of the Sun. And it's downright ironic to think of the cloistered convent of Santa Catalina occupying the same site as the equally cloistered Acllawasi, the home of the Inca chosen women, who were selected to serve the Sun in the Qorikancha temple. The cultural combination appears in countless other ways: witness the pumas carved into the cathedral doors. The city also gave its name to the Escuela Cusqueña (Cusco School) of art, in which new-world artists combined Andean motifs with European-style painting, usually on religious themes. You'll chance on paintings that could be by Anthony Van Dyck but for the Inca robes on New Testament figures, and Last Supper diners digging into an Andean feast of vizcacha (a type of chinchilla) and fermented corn.

The Río Urubamba flows, at its closest, about 30 km (18 miles) north of Cusco and passes through a valley about 300 meters (980 feet) lower in elevation than Cusco. The northwestern part of this river basin, romantically labeled the Sacred Valley of the Inca, contains some of the region's most appealing towns and fascinating pre-Columbian ruins. A growing number of visitors are heading here directly upon arrival in Cusco to acclimatize. The valley's altitude is slightly lower and its temperatures are slightly higher, making for a physically easier introduction to this part of Peru.