On the stand she explained that, under intense police interrogation, she had "imagined" hearing the scream.
Wearing white and sporting a ponytail, Knox explained to the jury in a confident voice why she signed a statement at a Perugia police station implicating herself, a statement she now says was false.
"They got tough with me, called me a liar and said I was trying to protect someone," Knox said in English with an Italian translator standing by her side. She spoke in a confident voice and used her hands freely to emphasize her points.
She later switched to Italian, expressing frustration with the translation.
"I wasn't trying to protect anyone, so I didn't know how to respond," Knox said. She added, "I couldn't understand why they were so sure I was the one who knew everything."
She said police posed the same questions over and over again, repeatedly asking her who she thought had killed her roommate and asking her to go over exactly what she did the night Kercher died.
At one point, Knox told the jury, police hit her on the head.
"I was hit in the back of the head by one of the police officers who said she was trying to make me -- help me remember the truth," Knox said.
The Perugia police have repeatedly denied any misconduct on the night of the interrogation or at any other point.
The prosecution maintains that the confused testimony Knox gave to the police is a sign of her culpability.
Knox arrived at the courthouse to a crush of photographers and reporters from around the world.
She smiled briefly at her family, but otherwise looked serious and tense.
When describing the day the murder was discovered, her voice cracked with emotion, as if she were going to cry. She said police were in the house that day, and she was cold, so she went to a car. Sollecito came out to tell her that Kercher had been knifed. Knox recalled thinking it was "too much," and crying.
Ted Simon, a prominent criminal defense lawyer, told ABC's "Good Morning America" that the pressure was on Knox to explain herself to the jury and present herself as a believable witness. That was key to the decision over which language to speak in.
Although Knox was supposed to be a defense witness, the judge allowed lawyers representing a civil case filed against Knox to question her first.
"In effect, she started with hostile questioning and she turned to English," Simon said about Knox, who is fluent in Italian and had originally planned to testify in Italian.
"She has to clearly communicate her explanation, and she also has to communicate her very being, that she herself is inconsistent with the heinous crime that's being charged," Simon told "GMA."
Her switch to English showed the danger she faces in testifying, Simon said.
"This is the risk of taking the stand, especially in a foreign venue," he said. "She had to switch from one language to another. She didn't like the interpreter. She thought this is getting lost in translation. And she starts off with all guns on her. A lot of pressure."
Amanda's father, Curt Knox, who was in the courtroom, said Knox's testimony would vindicate her.
"People are going to get a different picture of who Amanda really is," he told reporters. "She is just a regular kid, not a dark angel or whatever they want to call her."