The Ukrainian-born Demjanjuk is expected to be pushed into the Munich court in a wheelchair to face 27,900 individual charges of assisted murder while a Nazi guard at Sobibor in occupied Poland between March and September 1943.
If found guilty, the infirm elderly man will almost certainly spend the rest of his life in prison. If acquitted, he will face an uncertain future as he has no passport and no country wants him.
Demjanjuk, deported from the United States in May after a decades-long cat-and-mouse game with justice, denies even being at Sobibor, where an estimated 250,000 men, women and children perished in the gas chambers.
But prosecutors have an SS identity card bearing his name and his transfer orders from Trawniki, a sadistic training camp for Nazi guards, to Sobibor.
Israeli and US courts have already established he was there.
More than 30 co-plaintiffs are expected to be in Munich, most of whom lost family members at the camp. There are no living eyewitnesses who saw Demjanjuk there, so prosecutors will rely heavily on testimony by people now dead.
The court has set aside the first three days to hear 19 of the co-plaintiffs. Demjanjuk will be given the opportunity to speak on Monday but it was unclear whether he would.
Demjanjuk says he was a Red Army soldier captured in 1942 by the Germans and then moved around various prisoner-of-war camps. After the war, he moved to the United States, where he was a car worker in Ohio.
"We know in our hearts that my dad never harmed anyone. And we know based on the evidence that there is absolutely no evidence that he harmed even one person," his son, John Demjanjuk Jr., said.
Demjanjuk's lawyer, Ulrich Busch, said that even if it could be proved his client was at Sobibor, he would have been there under duress and cannot now be held responsible for the atrocities carried out there.
Demjanjuk, who turns 90 in April, is suffering, his family says, from a litany of health complaints, including bone marrow disease and blood infections, and is confined to a wheelchair.
His poor health means that proceedings will be limited to two 90-minute sessions per day, and his defence team has called for the trial to be shortened and held behind closed doors due to Demjanjuk's susceptibility to infection.
"They've accelerated his death... he's not going to survive this," his son said.
The trial, in the southern German city of Munich, is not the first time the barrel-chested, round-faced Demjanjuk has been in the dock for war crimes.
He was sentenced to death in Israel in 1988 for being "Ivan the Terrible", a particularly sadistic Nazi guard, but after five years on death row the conviction was overturned when it emerged that Israel had the wrong man.
For Efraim Zuroff, head of the Simon Wiesenthal Centre in Jerusalem, the Jewish organisation that hunts Nazi war criminals, the trial is a seminal moment.
"He is the most wanted Nazi criminal, top of the list we publish ... we will finally know his exact role in the extermination machine," Zuroff said.
"All I want is for justice to be done. Nothing else," Kurt Gutmann, a co-plaintiff whose mother and brother were murdered at Sobibor, said.