In the statement, presented to the appeals court in Florence by Knox's lawyer, Luciano Ghirga, the American student insisted she had done nothing wrong.
"I must repeat to you. I'm innocent. I did not rape, I did not steal ... I did not kill Meredith," Knox said.
The retrial began in September without either Knox or her former boyfriend and fellow accused Raffaele Sollecito in court. Both have maintained their innocence.
The presiding judge, Alessandro Nencini, read aloud Knox's statement Tuesday.
In it, Knox said "there is no scientific proof that puts me in the crime scene" and that Kercher's killer had left enough traces behind for the court to be satisfied it was not her.
"It is impossible to identify and destroy genetic traces and leave others. I was not there," she said.
Knox said that her behavior after Kercher's murder was discovered, when she could have left the country but instead stayed to help the investigation, also demonstrated she was not involved in the killing.
She complained of her treatment by police, saying she had been lied to, threatened and hit by them.
Knox also told the court that she had endured psychological pressure during her first murder trial, in 2009, because she was called many things.
"'I was called a wolf in sheep's clothing, a rapist, a thief, psychotic... Try to imagine your 20-year-old daughter being called all these things," she said. "I am not psychotic. I don't have a split personality."
Sollecito and Knox were convicted in 2009 of killing Kercher, 21, who was found stabbed in November 2007 in the villa that she and Knox rented in the central Italian university town of Perugia.
Their convictions were overturned in 2011 for "lack of evidence." But Italy's Supreme Court decided last year to retry the case, saying that the jury that acquitted them didn't consider all the evidence and that discrepancies in testimony needed to be answered.
Prosecutor Alessandro Crini last month said both Knox and Sollecito should be convicted and handed a 26-year sentence for homicide, with an additional four years for Knox for slander.
Knox's lawyer called Tuesday for her "acquittal verdict... to be confirmed."
A lawyer for Kercher's family, Francesco Maresca, gave his closing remarks Monday.
"No one remembers Meredith, while the two defendants write books, speak to the media and earn money," Maresca said.
The defense for Sollecito may present its arguments next month.
Knox returned to her hometown of Seattle after her acquittal and has been living there since. She says she is afraid to return to Italy, where she spent four years behind bars.
Ivory Coast citizen Rudy Guede has been convicted and sentenced for his role in Kercher's murder.
CNN's Hada Messia reported from Rome and Laura Smith-Spark wrote in London.