El Shafee Elsheikh, 33, stands accused of hostage-taking and conspiracy to commit murder as part of a group of Islamic State militants, known as the Beatles for their British accents.
But in court on Wednesday, Mr Elsheikh claimed he was not part of the group.
The group is said to have tortured and beheaded hostages in Syria, including several journalists and aid workers.
Prosecutors alleged Wednesday that Mr Elsheikh was in fact close friends with the other members and took part in their "unrelenting and unpredictable abuse". Their evidence will show he was involved in ransom demands from the families of hostages.
The Sudanese-born Londoner, who was stripped of his British citizenship in 2018, is charged with taking hostages, resulting in the deaths of four Americans - journalists James Foley and Steven Sotloff and aid workers Kayla Mueller and Peter Kassig.
He is also charged with conspiring in the deaths of the British aid workers David Haines and Alan Henning, and Japanese journalists Haruna Yukawa and Kenji Goto.
His trial, in Virginia, is expected to last three to four weeks.
The defence told the court that Mr Elsheikh was always fully masked when around hostages. It will seek to show that government evidence identifying Mr Elsheikh is "inconsistent and unconvincing".
They also asserted that, because he was a "simple ISIS fighter" and not a Beatle, he could not be held legally responsible for the actions of others.
In the courtroom - Nomia Iqbal, BBC News, Virginia
Most of the families of the hostages who died were in court and comforted each other as El Shafee Elsheikh entered the courtroom.
He was wearing a blue shirt and black glasses, and sporting a long beard. A black Covid mask covered his face, which he will have to remove at points during the trial when asked to identify himself.
In fact identification is at the heart of the defence's case. Mr Elsheikh's lawyer kept his opening statement short, saying that this was a "horrific and heart-breaking" case which the jurors may find it hard to keep an open mind on. But he also said Mr Elsheikh was not a member of the so-called Beatles and that "evidence will show inconsistencies" from witnesses about his identity.
Mr Elsheikh has previously attributed the planning and killing of hostages to fellow Beatle Mohammed Emwazi.
Emwazi, known as Jihadi John, was thought to be the group's ringleader. He was killed by a joint US-UK drone strike in Syria in 2015.
The other two Beatles - Aine Davis or "Paul" and Alexanda Kotey or "Ringo" - are in custody in Turkey and the US respectively.
Together, the group is alleged to have abducted at least 27 people and "engaged in a prolonged pattern of physical and psychological violence against the hostages", including by electric shocks, mock executions and waterboarding.
Hostages called Mr Elsheikh "George" and say that as the main guard he carried out most of the torture.
More than 50 witnesses are expected to take the stand against him.
Four rows of seats in the courtroom will be permanently reserved for former hostages and their families.
The James Foley Foundation on Tuesday applauded the beginning of the trial, saying the late Foley had been used as propaganda and murdered.
"Hostage takers must be held accountable to deter further hostage taking. Too often captors of US nationals evade arrest and indictment, and therefore never face justice," it said.