The indictment accuses Ahmed al-Asiri, ex-deputy chief of Saudi intelligence, and Saud al-Qahtani, a former adviser to Saudi Crown Prince Mohammed bin Salman (MBS), of "instigating premeditated murder with monstrous intent."
Khashoggi was murdered inside Riyadh's consulate in Istanbul on Oct. 2, 2018. He was getting papers to marry his Turkish fiancée Hatice Cengiz, who was waiting outside.
Eighteen others are accused of carrying out the killing with "monstrous intent and torture."
Khashoggi was strangled to death and his body dismembered, the indictment seen by German Press Agency (DPA) says.
The remains of the Washington Post columnist, who was once close to the royal family but became a vocal critic of MBS, were never found.
The prosecutor is seeking aggravated life sentences for all, the harshest term in Turkey since it abolished the death penalty in 2002.
The indictment was based on analysis of mobile phone records of the suspects, records of their entry to and exit from Turkey, records of their presence at the consulate, witness statements and analysis of Khashoggi's phone, laptop and iPad, a statement by the prosecutor's office said.
The evidence includes statements by Cengiz, who will attend the hearing with Agnes Callamard, the U.N. special rapporteur on extrajudicial killings who investigated Khashoggi's death.
In December, Riyadh said five people were sentenced to death for the murder after a trial shrouded in secrecy. Khashoggi's sons subsequently said they forgave his killers, paving the way for a reprieve.
The Istanbul trial "represents the best hope for justice" for Khashoggi "following a blatant miscarriage of justice in the Saudi courts," said Erol Önderoğlu, Turkey representative for media watchdog Reporters Without Borders.
"I hope this criminal case in Turkey brings to light the whereabouts of Jamal's body (and) the evidence against the killers," Cengiz told Reuters.
Cengiz said neither the trial nor the pardon followed due process. "No one can take the 'trial' that took place in Saudi Arabia legitimately; it was done in secret and the individuals sentenced are unnamed," Cengiz said.