He is a member of one of the paramount Families of State (Aiga Tupu) where he holds the Tupua title of the SaTupua 'royal' family. He also holds the Tama-a-Aiga Tamasese title and the Tafaifa title of Tui Atua. He first entered parliament and became Prime Minister under the title Tupuola.
Tupua attended primary school at the Marist Brothers School at Mulivai in the Samoan capital of Apia. He continued his education at St. Patrick's College in Silverstream, Wellington, New Zealand. He was also educated at Victoria University of Wellington, located in New Zealand's capital city.
Tupua has been described as a defender and proponent of the Samoan language.
Tupua served as Prime Minister for two consecutive terms from 1976 to 1982. He also served as Deputy Prime Minister from 1985 to 1988. It was during his second term as Prime Minister that the Public Service Association went on a general strike in 1981, paralysing the country for several months and paving the way for the opposition Human Rights Protection Party's entry to government in 1982. The Human Rights Protection Party still governs Samoa today.
Tupua became Leader of the Opposition following his Christian Democratic Party's election defeat in 1982. He also headed the Samoan National Development Party. He continued to serve Anoama'a East as MP until 2004 when he became one of the two member of Samoa's Council of Deputies along with Tuimalealiifano Vaaletoa. Both Efi and Vaaletoa served as temporary acting heads of state (O le Ao o le Malo) following the death of Malietoa Tanumafili II in May 2007.
Tupua has served as an adjunct professor for Awanuiorangi in New Zealand. He later went on to serve as an Associate Member of the Matahauariki Institute at Waikato University. Additionally, he has held a position as PhD examiner at Australian National University in Canberra for Pacific and Samoan history.
Tupua has helped to begin excavations at Samoa's important Pulemelei Mound archaeological site. Samoans, under Tupua Tamasese, carried out a ceremony to honor Thor Heyerdahl for his contributions to Polynesia and the Pulemelei Mound excavations in 2003.