A whoop of joy was heard in the court as the ruling overturning their sentences was read out but Knox herself broke down and was led out sobbing and supported by police officers.
"As you could see from the images, Amanda was a nervous wreck who just collapsed. She wasn't able to say anything other than 'thank you' in a flood of tears," one of her lawyers, Maria Del Grosso, told reporters.
Speaking to a crowd outside the courtroom, Knox's sister Deanna thanked her legal team and supporters.
"We're thankful that Amanda's nightmare is over. She suffered for four years for a crime she did not commit," she said. "We are also thankful to the court for having the courage to look for the truth and to overturn the conviction."
The verdict, a severe embarrassment to the Italian justice system, came after independent forensic investigators sharply criticized police scientific evidence in the original investigation, saying it was unreliable.
Kercher's half-naked body, with more than 40 wounds and a deep gash in the throat, was found in 2007 in the apartment she shared with Knox in the Umbrian hill town of Perugia where both were studying.
Both Knox and Sollecito, 27, consistently had maintained their innocence throughout the original investigation and trial. A third man, Ivorian drug dealer Rudy Guede, was imprisoned for 16 years for his role in the murder.
Knox returned briefly to the Perugia jail where she had been held to complete formalities before being driven away to an unknown destination in a black Mercedes with shaded windows.
She is expected to return to the United States Tuesday although it was not immediately clear whether she would be returning on a regular flight or on a private plane.
Sollecito, who had been held in a separate jail near Perugia, also left custody but his lawyer refused to say where he would be spending his first night of freedom.
"It was obvious that he had nothing to do with the death of that poor girl," Sollecito's father, a doctor, said after the verdict which he said had "given me back my son."
The court upheld a conviction against Knox for slander, after she had falsely accused barman Patrick Lumumba of the murders. It sentenced her to three years in prison, a sentence which she has now already served.
