In his closing arguments in the year-old trial, defense lawyer Carlo Dalla Vedova told jury members it was their duty to clear the American of all charges because the prosecution's case was flawed.
"If there is any doubt, if the evidence is not serious, reliable and coherent, I urge you to clear this girl," he said.
In nearly six hours of remarks, Dalla Vedova charged that key DNA evidence in the case cannot be attributed "beyond any doubt."
"There are still many doubts in this trial, and there's a young girl waiting to be judged," he told the eight-member jury, which is expected to issue a verdict Friday or Saturday.
The Seattle-born Knox and her former Italian boyfriend Raffaele Sollecito are being tried in Perugia, central Italy, for the slaying of Meredith Kercher. Both deny wrongdoing.
Perhaps reflecting that the end game has begun, a quite different-looking Knox entered court today, reports CBS News correspondent Allen Pizzey from Perugia. Gone was the flowing hair and bright shirts. Some observers noted that the severe image is one Knox would have been better adopting throughout the year-long trial.
Knox is expected to address the court before the final rebuttals, Pizzey adds.
Kercher's body, her throat slit, was found in a pool of blood on Nov. 2, 2007, in the apartment she shared with Knox in Perugia. Prosecutors argued that Knox resented her British roommate and killed her, together with Sollecito and Rudy Hermann Guede of Ivory Coast, under "the fumes of drugs and possibly alcohol."
Prosecutors say a knife with a 6 1/2-inch (16.5-centimeter) blade, with Kercher's DNA on the blade and Knox's on the handle, was found at Sollecito's house.
Defense lawyers have argued that the knife is too big to match Kercher's wounds and claim the amount of what prosecutors say is Kercher's DNA is too low to be attributed with certainty.
Dalla Vedova also countered prosecutors' claim of a possible motive for the slaying. Prosecutors have charged Knox wanted to get back at Kercher for saying she wasn't clean and was promiscuous.
"We need facts, not only vague statements," said Dalla Vedova, who contended that any such resentment couldn't explain the violent killing.
He also contended that it had not been proved in court that Knox, Sollecito and Guede had plotted an attack on Kercher. "It needs to be proven that the three knew each other, had made arrangements, telephone calls, contacts," he said. "There must have been some sort of preparation. You don't carry out such a gruesome killing with people you don't know."
Prosecutors contend that Knox, Sollecito and Guede met at the apartment before the killing, possibly to settle some drug issues with the Ivorian.
Dalla Vedova portrayed Knox as a "clean-faced young girl, swept away by a tsunami." He noted she decided not to go back to the United States as she could have in the days after the slaying.
After the hearing, Knox's father Curt, who sat behind his daughter in court together with her mother Edda Mellas and other family members, told reporters that Knox is "hanging in there, actually doing quite well."
Tuesday's hearing was "a step in the right direction, and it continues to break down the prosecution case and proves that Amanda and Raffaele are innocent," he said.
Kercher's family lawyer Francesco Maresca told reporters that evidence presented in the case is solid and expressed confidence the two defendants would be convicted. He said Kercher's family members were expected to travel to Perugia on Friday for the verdict's announcement. Another lawyer for Knox, Luciano Ghirga, is scheduled to take the stand Wednesday.
Knox, 22, and Sollecito, 25, have been jailed for more than two years since being arrested shortly after the slaying. They are being tried on charges of murder and sexual violence and prosecutors have urged they be given life imprisonment - Italy's stiffest punishment. Both were in court Tuesday.
Guede was sentenced to 30 years in prison last year after a fast-track trial he had requested. He also denies wrongdoing and is appealing his conviction.
Knox and Sollecito maintain they spent the night of the murder at Sollecito's house in Perugia, watching a movie on his computer and smoking pot. Their defense lawyers are working on the theory that Guede was the sole attacker.