Nast deputy digital editor Laura Redman tells CNN.
"Europeans are heading to Charleston because they've heard about the food and the architecture. It's getting great press, and it's having a moment."
Sydney came in second place, followed by Dublin in third place.
More than 100,000 readers responded to the travel magazine's reader survey of favorite cities, hotels, resorts, islands, airlines, cruise lines, future travel destinations and, for the fourth year in a row, reader opinions of the world's friendliest cities.
To arriving travelers, a city can get a reputation for friendliness through its locals and its appearance.
Charleston, Savannah and Nashville, all southern US cities, stand out as spots where locals are quick to offer directions and other assistance -- and where the locals talk to each other.
"They haven't lost their Southern charm," says Redman.
Hotel or resort staff greeting guests on arrival with an easy check-in process and refreshing beverages, sometimes specifically for the children, also stands out.
Cities that are easily navigable and offer guests the chance to feel like a local also feel friendly to visitors, she says.
Conde Nast Traveler's top 10 friendliest cities
1. Charleston, South Carolina
2. Sydney, Australia
3. Dublin, Ireland
4. Queenstown, New Zealand
5. Park City, Utah
6. Galway, Ireland
7. Savannah, Georgia
8. Krakow, Poland
9. Bruges, Belgium
10. Nashville, Tennessee