Robert Sylvester Kelly is accused of racketeering, sexual abuse and bribery. Kelly has denied all these charges.
If he is convicted on all counts he could be sentenced to several decades in prison.
Some of the allegations date back more than 20 years and include Kelly requiring victims to demonstrate “absolute commitment” and to obey strict rules such as not be allowed to eat or drink and go to the bathroom until he grants them permission.
Also, they allegedly were required to call him Daddy.
Opening statements were delivered to a jury of seven men and five women, who will decide the 54-year-old singer's fate.
Kelly faces charges that he was the ringleader of a two-decade scheme where he recruited women and underage girls for sex.
US prosecutor Maria Cruz Melendez told the jury in an opening statement that the case is "about a predator.”
Kelly was previously acquitted in 2008 in a child pornography case in Chicago.
The recent trial is the culmination of years of suspicions and accusations against Kelly discussed in the Lifetime 2019 documentary Surviving R Kelly.
The series explored how an entourage of supporters protected Kelly and silenced his victims for decades, foreshadowing a federal racketeering conspiracy case that landed in Kelly in jail in 2019.
Female accusers are also expected to offer evidence about how Kelly's managers, bodyguards and other employees helped him recruit women and girls, and sometimes boys, for sexual exploitation.
Defence lawyers have countered by saying Kelly's alleged victims were groupies who turned up at his shows and made it known they "were dying to be with him".
The women only started accusing him of abuse years later when public sentiment shifted against him, they said.
The trial, coming after several delays due mostly to the pandemic, unfolds under coronavirus precautions restricting the press and the public to overflow courtrooms with video feeds.
The New York case is only part of the legal battle facing the singer.
He also has pleaded not guilty to sex-related charges in Illinois and Minnesota.