A self-styled mystic and prophet, Kony sought to impose his own version of the Ten Commandments on northern Uganda
Ongwen, now in his early 40s, will also be the first former child soldier to be tried by the tribunal and is due to plead to an unprecedented 70 counts of war crimes and crimes against humanity committed by the rebel group led by the elusive Joseph Kony.
"The LRA leadership is reviled worldwide for its brutality against Africans, but never before has an LRA commander faced trial," said Elise Keppler of Human Rights Watch, calling the trial a "significant first".
A self-styled mystic and prophet, Kony sought to impose his own version of the Ten Commandments on northern Uganda after founding the LRA in 1987.
The UN says it has slaughtered more than 100,000 people and abducted 60,000 children since it launched a bloody rebellion against Kampala.
More than 4,000 victims are taking part in Ongwen's trial and thousands of others are expected to watch the trial unfold at four viewing sites in northern Uganda.
"Victims of LRA crimes have been waiting for justice for up to 14 years," said Sheila Muwanga, vice president of the International Federation for Human Rights.
Victims have recounted the LRA's sadistic initiation rites for kidnapped youngsters, who were forced to bite and batter friends and family to death, or to drink their blood.
The son of Ugandan schoolteachers, Ongwen was abducted as a child while on his way to school and press-ganged into the militia's ranks. He likely endured such horrors himself.
But ICC prosecutors say when Ongwen became an adult he turned abuser, helping orchestrate the abduction and enslavement "of children under the age of 15 to participate actively in hostilities".
He stands accused of rape, murder and "forced marriage" -- the first such charge at the ICC -- as well as the unprecedented legal charge of "forced pregnancy".
While boys ended up in the ranks, girls were "treated as spoils of war" and turned into sex slaves.
Ongwen is said to have had at least seven wives -- one was just 10 when she was first raped. DNA tests have revealed he fathered at least 11 children with different girls.
Prosecutors also allege that from 2002 to 2005, Ongwen "bears significant responsibility" for attacks in northern Uganda, "systematically" ordering the killings of civilians sheltering in four camps.
Victims died in an orgy of violence, while survivors had their lips and ears cut off. In one case, a witness said Ongwen ordered his troops to cook and eat civilians.
The defence however says it is considering several arguments including that Ongwen is suffering from post-traumatic stress syndrome. His lawyers also maintain he was acting under duress, as he lived under the constant threat of being killed by Kony and his commanders.
Prosecutors intend to bring 74 witnesses including former child soldiers and some 5,800 pieces of evidence such as intercepted radio communications, videos and photos.
Observers say Ongwen's trial raises deep questions about how to prosecute crimes involving children subjected to years of abuse who then turn perpetrators. The case is likely to set a legal precedent.
"Dominic Ongwen's past experience as a child soldier is not a defence in itself," said Isabelle Guitard, programme director at the London-based Child Soldiers International.
"It cannot exonerate him of the responsibility of having committed war crimes and crimes against humanity as an adult," Guitard told AFP.
Human Rights Watch activist Keppler said the fact that Ongwen was a child soldier is "an important and relevant piece of the trial, of his story".
After this week's opening, the trial is set to resume on January 16 and is expected to last several years.
Ongwen surrendered himself to US forces in 2015. But Kony remains at large with about 150 followers hiding out in the jungles of the Central African Republic.