James Dixon, 24, of Clinton Hill, was indicted for manslaughter and felony assault in relation to Nettles' death, prosecutors said Tuesday in Manhattan Criminal Court.
Dixon was held without bail and said nothing. He pleaded not guilty to the charges.
"I'm overwhelmed," Delores Nettles, the victim's mother, told DNAinfo New York. "I still want to know the facts, but it's been a long time coming."
The reason for the delay in charging Dixon was not clear, but investigators say they struggled because witnesses were not able to tell him and another man who was arrested for the crime, Paris Wilson, apart.
According to prosecutors, Dixon was among a group of seven young men who ran into Nettles, 21, and two transgender friends who were walking down Frederick Douglass Boulevard near 148th Street the night of Aug. 17, 2013, just across the street from a NYPD housing bureau precinct.
The men became enraged once they discovered that Nettles was transgender, according to prosecutors and a fight broke out.
Dixon punched Nettles in the face, making her to fall to the ground and strike her head on the sidewalk, causing a serious brain injury, said Assistant District Attorney Nicholas Viorst.
Viorst alleges that Dixon brutally beat Nettles and "struck her repeatedly as she lay on the ground" while "driving the side of her head into the pavement."
The indictment charges that Dixon used the sidewalk as a "dangerous instrument" to cause Nettles' death.
Police discovered Nettles unconscious on the ground and rushed her to Harlem Hospital.
The case was initially treated as an assault, but Nettles' condition worsened and she slipped into a coma before being placed on life support.
Delores Nettles eventually removed her daughter from life support on Aug. 20.
On the same day, Viorst said that Dixon went to Wilson's home and told him that he "intended to take responsibility" for the beating.
Wilson's mother subsequently escorted Dixon to the police station where, according to prosecutors, he made written and video confessions to beating Nettles.
That threw the case into confusion. Prosecutors believed Wilson was the attacker.
But because Wilson and Dixon bear a "striking resemblance" to one another, prosecutors say witnesses to the attack identified both Wilson and Dixon as the assailant.
According to court documents, Dixon made his statements to officers at the 32nd Precinct on Aug. 21, 2013.
The confusion prevented the district attorney's office from bringing the case before a grand jury. The office pleaded with the public for additional witnesses to come forward and said new witnesses were likely the only thing to be able to move the case forward.
All charges against Wilson were dropped. Prosecutors said in court Tuesday that Wilson was part of the group of seven men who encountered Nettles but that he did not attack her.
The prosecutor's office declined to explain what has changed in the case in the 17 months since Dixon allegedly confessed to beating Nettles.
"These are some pretty unique circumstances," Viorst said in court.
City Council Speaker Melissa Mark-Viverito, Harlem Councilwoman Inez Dickens and the council's LGBT Caucus praised the arrest.
“LGBTQ New Yorkers—very often transgender women of color like Islan Nettles—are too often the targets of attacks and the City Council stands in solidarity with them as we work to ensure all communities are treated with respect," they said in a statement.
Manhattan District Attorney Cyrus Vance Jr. said his office has doggedly pursued the case.
“Over the past 18 months, my office has exhaustively investigated this case with the primary objective of making sure that justice is served for Islan Nettles,” Vance said In a statement.