Her co-defendant, former boyfriend Raffaele Sollecito, was convicted and sentenced to 25 years. The two also were found guilty of sexual assault in the 2007 murder of Meredith Kercher, a 21-year-old student from England.
"No, no," Knox said, bursting into tears and clinging to one of her lawyers as the judge read the verdict just after midnight following some 13 hours of deliberations.
Minutes later, the 22-year-old Knox, who is from Seattle, and the 25-year-old Sollecito were put in police vans with sirens blaring and driven back to jail.
Prosecutors had sought life imprisonment, Italy's stiffest sentence. Courts can give less severe punishment than what prosecutors demand.
The American's father, Curt Knox, asked if he would fight on for his daughter, replied, with tears in his eyes: "Hell, yes."
"This is just wrong," her stepmother, Cassandra Knox, said, turning around immediately after hearing the verdict. Her family had insisted she was innocent and a victim of character assassination.
The family said later in a statement they would appeal the ruling.
One of Knox's attorneys, Luciano Ghirga, was asked if she was distraught. "Yes, I challenge anyone not to be," he replied.
Silence fell on the packed and tense courtroom as the jurors walked in. Kercher's mother and sister cried at the verdict.
"The sentence is fair and satisfactory for the family," said their lawyer, Francesco Maresca. "It was a heartfelt sentence. There is deep suffering on all sides."
A juror, a woman, also looked like she was crying after the verdict.
A group of local youths who gathered outside the courthouse shouted insults and "assassin!" at the Knox family as they walked in to hear the verdict.
Throughout the trial, prosecutors depicted Knox as a promiscuous and manipulative she-devil whose personality clashed with her roommate's. They say Knox had grown to hate Kercher.
The most intimate details of Knox's life were examined, from her lax hygiene - allegedly a point of contention with Kercher - to her sex life, even including a sex toy.
"It appears clear to us that the attacks on Amanda's character in much of the media and by the prosecution had a significant impact on the judges and jurors and apparently overshadowed the lack of evidence in the prosecution's case against her," the statement said.
The eight-member jury was not sequestered during the trial.
In Seattle, relatives and friends clasped hands as they watched the verdict on TV. "Oh God, no," her uncle, Mick Huff, cried when it was announced.
Other friends buried their faces in their hands and shook their heads.
"They didn't listen to the facts of the case," said Elisabeth Huff, Knox' grandmother. "All they did was listen to the media's lies."
Madison Paxton, Knox's friend from the University of Washington, said: "They're convicting a made-up person ... "They they're convicting 'foxy Knoxy.' That's not Amanda."
Prosecutors argued that on the night of the murder, Knox and Sollecito met at the apartment where Kercher and Knox lived. They say a fourth person was there, Rudy Hermann Guede, an Ivory Coast citizen who has been convicted in the murder and sentenced to 30 years in prison. Guede, who is appealing his conviction, says he was in the house the night of the murder but did not kill Kercher.
The prosecution says Knox and Kercher started arguing, and that Knox joined the two men in brutally attacking and sexually assaulting the Briton under "the fumes of drugs and possibly alcohol."
Knox said Kercher was a friend whose slaying shocked and saddened her.
Defense lawyers described the American, who made the dean's list at the University of Washington, as a smart and cheerful woman, at one point even comparing her to film character Amelie, the innocent and dreamy girl in the 2001 French movie of the same title.
That is the film Knox and Sollecito said they were watching at his home on the night of the murder, where they say they smoked marijuana and had sex. Knox said she went home the next morning to find the door to the house open and Kercher dead.
The prosecution said a 6½-inch (15.2-centimeter) knife authorities found at Sollecito's house had Kercher's DNA on the blade and Knox's on the handle. Defense lawyers said the knife was too big to match Kercher's wounds and the amount of DNA collected was too small to determine with certainty whose it was.
The defense maintained there was not enough evidence for a conviction and no clear motive.
However, prosecutor Manuela Comodi said violent crimes can lack a motive. "We live at a time where violence is purposeless," she told the jury.
The pair also was convicted of illegally carrying a weapon - the knife - and of staging a burglary at the house where the murder occurred by breaking a window, supposedly in an effort to sidetrack the investigation.
Knox also was convicted of defaming a man she had originally implicated in the case.
After the murder, Knox told investigators she was home and had to cover her ears to block out Kercher's screams. She accused a Congolese man, Patrick Diya Lumumba, of the killing. Lumumba, who owns a pub in Perugia where Knox worked, was jailed briefly but was later cleared. Knox said during the trial that police pressure led her to initially accuse an innocent man.
Associated Press writer Gene Johnson in Seattle contributed to this report.