The mission circuit begins and ends in Santa Cruz de la Sierra, Bolivia's largest lowland city and the main access point by air or bus. From there, the route runs east in a rough loop: Santa Cruz to San Javier (225 km on good paved road, three to four hours), then to Concepción (80 km on a paved but winding road, about 90 minutes), and onward to San Ignacio de Velasco on that infamous red sand track. San Ignacio serves as the commercial hub and base for visiting three smaller missions — San Rafael, San Miguel, and Santa Ana — which lie on their own loop roughly 40 kilometers apart. San José de Chiquitos, the southernmost mission, can be reached from San Ignacio by a 230-kilometer sand track or from Santa Cruz by overnight bus or train. A non-four-wheel-drive car can handle the clockwise route in dry season. In the wet, all bets are off.

Each mission town is organized around its church, and each church is different. San Javier's sits just 50 meters off the main road, with its Spanish inscription above the door. Concepción's cathedral, a few blocks from the bus stop, houses a music archive where thousands of baroque scores were discovered during restoration work in the 1970s. Santa Ana de Velasco preserves the most faithful original layout: an open grassy plaza, unchanged since colonial times, facing a church built entirely by the indigenous population after the Jesuits' expulsion. Inside that church sits the only original organ in the Chiquitos missions, carried from Potosí by mule over 1,000 kilometers in 1751. The organ still works. San Miguel, San Rafael, and Santa Ana can theoretically be visited as a day trip from San Ignacio by taxi for around 400 bolivianos, but public transport between the three is rare enough that missing a bus may mean spending an unplanned night.

The best time to visit depends on what you want. For nature, locals recommend December, when the vegetation turns lush and green. For the most powerful church experience, time your visit to coincide with the International Baroque Music Festival, held every two years. During the festival, musicians from around the world perform baroque compositions inside the mission churches — some of them works recovered from the very archives hidden in these buildings for centuries. Live harpsichord and choral music echoing through wooden naves built by indigenous carpenters in the 1700s is not an experience that translates easily into words. The towns also host their own local festivals throughout the year, and doing advance research to align your visit with one of these can transform a historical tour into something alive and immediate.

The Chiquitania is more than its missions. The region boasts rivers, lagoons, hot springs, caves, and waterfalls, though tourism infrastructure for these natural attractions remains limited. Between San José de Chiquitos and Santiago de Chiquitos, the town of Chochís offers a sanctuary and a rock formation locals call the "devil's thumb." From San José, the railway once ran to the Brazilian border at Quijarro, connecting to Corumbá and the southern Pantanal — though the line has been suspended since 2020. North of the circuit, Noel Kempff Mercado National Park offers world-class wildlife but difficult access. The tourist information office in San Ignacio discourages hitchhiking on trucks for safety reasons, which gives you a sense of how far from conventional tourism this corner of Bolivia remains. Accommodation exists in all mission towns, with the best hotels in Concepción and San Ignacio. Outside festival season, finding a room is rarely a problem.