The MPLA, which has ruled since Angola's independence from Portugal in 1975, is expected to defeat opposition parties, which are stifled by Dos Santos's authoritarian regime.
Dos Santos's unexpected retirement -- reportedly prompted by poor health -- has triggered the biggest political transition in decades for Angola, a leading oil exporter in Africa.
His chosen successor however is Defence Minister Joao Lourenco, a loyalist expected to avoid immediate change in a government often criticised for corruption and its failure to tackle dire poverty.
"If I succeed, I would like to be recognised in history as the man of Angola's economic miracle."
Dos Santos's long reign has seen the end of Angola's bloody civil war that lasted from 1975 to 2002, and a post-war investment boom as the country exploited its oil reserves.
But the flood of money brought little benefit to Angola's poor, and government spending collapsed when oil prices fell in 2014.
Inflation hit 40 per cent at the end of last year, when annual growth was less than one per cent.
AFP reporters witnessed a slow start to voting at one station in Luanda where Dos Santos and Lourenco are scheduled to cast their ballots later today.
At a weekend rally in front of thousands of MPLA supporters, Dos Santos, a frail-looking 74, made a brief appearance to endorse Lourenco.
"Dos Santos brought forward his departure to after these elections due to his deteriorating health," Alex Vines, of the Chatham House think tank, told AFP.
Dos Santos has been dogged by reports of illness. His regular visits to Spain for "private" reasons fuelled criticism that the state of his health was being hidden from ordinary Angolans.
Earlier this year, his daughter Isabel -- who has become a billionaire and Africa's richest businesswoman under his rule -- was forced to deny rumours he had died in Spain.
In the face of ruthless security force crackdowns and a biased state-run media, the opposition parties -- led by UNITA and Casa-CE -- have sought to tap into public anger at the government.
Samakuva, 71, took over UNITA after longtime rebel leader Jonas Savimbi was killed in 2002, a death that marked the beginning of the end of the civil war.
Dissent has often been dangerous under Dos Santos, who has been a secretive but inescapable presence in Angolan life for decades.
Angola's next leader "must guide the country out of the spiral of oppression," rights group Amnesty said in a statement.
Mateos Simon, 28, a former nurse, told AFP that he lost his job because the hospital was unable to pay him.
"I live in a house where there is no water, no electricity," he said. "The MPLA does nothing for us. Things have to change, now.
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