In the Samoan branch of Polynesian mythology, Upolu was the first woman on the island of the same name.
In 1841, the island was the site of the Bombardment of Upolu, an incident during the United States Exploring Expedition.
In the late-19th century, the Scottish writer Robert Louis Stevenson owned a 400-acre estate at Vailima village and died there in 1894. He is buried at the top of Mount Vaea above his former home. The Vailima estate was purchased in 1900 as the official residence for the German governor and, after British/Dominion confiscation, served successively as residence for the New Zealand administrator and for the Samoan head of state after independence.
An extremely small species of spider lives on Upolu. According to the Guinness Book of World Records, the spider is the size of a period on a printed page.
The island of Upolu was affected by a tsunami at 06:48:11 local time on 29 September 2009 (17:48:11 UTC). Twenty villages on Upolu's south side were reportedly destroyed, including Lepa, the home of Samoa's Prime Minister Tuilaepa Lupesoliai Sailele Malielegaoi. In Lepa, only the church and the village's welcome sign remained standing following the disaster.
Upolu was the filming location for the 1953 South Seas film Return to Paradise, starring Gary Cooper.
The island was also the filming location for several episodes of the CBS competitive Survivor reality television series: Survivor: Samoa, the nineteenth; Survivor: Heroes vs. Villains, the twentieth; Survivor: South Pacific, the twenty-third - and the twenty-fourth season, Survivor: One World. This makes it the most used location in the show's history.
Australian Survivor was also set on the island in the 2016 third season, and 2017 fourth season.