Santiago is one of the most visited cities in Chile and in South America. Depending where you're coming from, the city may be best reached by car, plane, and sometimes by bus.
From Punta Arenas
The distance between Santiago and Punta Arenas in Chile is 1877 miles (3,000 km). The best way to travel this route is to get on a plane. There are direct flights available so usually, you don't have to worry about transfers and stopovers which makes this a smooth trip.
The first step is to take a transfer or a bus to the Presidente Carlos Ibáñez del Campo International Airport (PUQ) in Punta Arenas. This takes about 20 minutes from the center. A flight will then take you to Santiago in 3.5 hours, or less and you'll land at the Santiago International Airport (SCL). From here you can take a bus, private transfer, or a taxi. You'll be in the city center in just 30 minutes.
It only takes 1.5 hours to get from Valparaíso straight to Santiago. That's why renting a car or booking a private transfer are the two best options here.
If renting a car then you can keep on route 68 for the entire journey. About 20 minutes after leaving Valparaíso, you'll get a chance to visit the Reserva Nacional de Lago Pelueñas—this is worth a stop if you've never been before. On the way, you'll also be passing by the famous wine region Casablanca Valley. Book a wine-tour before you leave Valparaíso or just explore the area by driving and walking around for a few hours.
From Buenos Aires
Visiting South America often includes visiting several major cities, such as Buenos Aires in Argentina. Getting from Buenos Aires to Santiago only takes 2.5 hours by plane and there is usually an abundance of flights available daily. The two main airlines for this trip are LATAM and Sky Airline.
You'll be starting the journey at the Ministro Pistarini International Airport (EZE). To get to the airport your best options are taking a taxi, a private transfer, or an airport shuttle. Getting to the airport by car only takes 20 minutes while airport shuttles take approximately 45 minutes and going by bys takes 1.5 hours.
Consider this 7-day itinerary in Buenos Aires and visiting the Iguazú Falls before leaving for Santiago.