Though seldom seen in public, he has been a looming presence in daily life for as long as most Angolans can remember, exercising almost total authority over government, politics, media and business.
Now aged 74, and in reportedly poor health, Dos Santos became president in 1979, making him Africa's second-longest serving leader -- one month shy of Equatorial Guinea's Teodoro Obiang Nguema.
He is set to stand down next year, according to state radio.
Until the 27-year civil war ended in 2002, Dos Santos presided over a country torn apart by conflict as his MPLA (People's Movement for the Liberation of Angola) government fought rebels led by the UNITA group.
He has been credited for leading Angola out of the war, moving away from hardline Marxism, and fostering a post-war oil boom and foreign investment surge that transformed central Luanda.
But his reign has also been criticised as secretive and corrupt, while Angola's citizens have suffered abject poverty as his family and the elite have become hugely wealthy.
Married to the glamorous former air hostess Ana Paula, who is 18 years his junior, his children include Isabel, who is head of the state-owned Sonangol oil company and reputed to be Africa's richest woman -- worth $3 billion.
Both Isabel and Dos Santos's son Zenu are spoken of as possible future presidents of the country.
"Against all odds, he has remained in power since 1979, overcoming challenges of war, elections and at the same time displaying a highly-refined political craftsmanship," said Alex Vines of the British think tank Chatham House.
He is "an accomplished and shrewd economic and political dealmaker with an instinct for political survival."
From humble beginnings as the son of a bricklayer, Dos Santos joined the MPLA as a teenager and rose quickly through party ranks as a fighter during Angola's struggle for independence from Portugal.
After stints in Kinshasa and Brazzaville, he went to Azerbaijan to study petroleum engineering and radar communications, returning fluent in Russian and French as well as his mother-tongue Portuguese.
In 1979 following the sudden death from cancer of Angola's liberation president Agostinho Neto, Dos Santos -- then planning minister -- was sworn in as president.
A presidential election in 1992 was aborted before a second-round vote when his battlefield rival Jonas Savambi claimed the vote was rigged.
The civil war reignited until Savambi was killed in 2002.
Another presidential election scheduled in 2008 was never held, and a new constitution in 2010 abolished direct election of the president.
The most recent parliamentary election in 2012 gave the MPLA another large majority and kept party leader Dos Santos securely in power.
During that election campaign, he made a series of unexpected appearances at public rallies, wearing colourful T-shirts and promising better universities and jobs for young people.
As head of the military, police and cabinet, the president has operated with few constraints.
He chooses the senior judges and has MPLA allies in all public agencies, including the supposedly independent electoral commission.
The state keeps a firm hand on the media and his picture often appears on the front page of newspapers, as well as on countless billboards and posters.
Angola has become a major supplier of oil to China, and Dos Santos has built close ties with the Asian giant.
While he presents himself a rock of stability, rights activists and opposition members accuse him of systematic repression.
Dissenters risk criminal charges and police crackdowns.
The oil boom -- which peaked with 20 percent GDP growth in 2007 -- has now faded sharply, leaving many of Luanda's new skyscrapers empty and little sign of benefits for Angolan people.
Among many dire statistics, Angola has the world's second highest mortality rate for children under five years old.
The always immaculately-dressed Dos Santos spends his time between his presidential palace in Luanda and a second residence south of the capital.
In a 2013 interview for Brazilian television, he declared that his rule had been "too long, too long," but added that decades of war "meant we couldn't strengthen state institutions or even carry out the normal process of democratisation."
Dos Santos, whose brother died last month, was reported to have received cancer treatment in Barcelona over several years.
He travelled rarely on official business while in office, but is said to enjoy music, poetry, cooking fish and was a keen footballer until injury stopped him playing.