Photo: Amanda Knox.
Her Italian ex-boyfriend Raffaele Sollecito was also convicted and sentenced to 25 years.
They were also convicted of sexual assault in the 2007 murder of Meredith Kercher, a 21-year-old student from England.
The verdict was reached after nearly 12 hours of deliberation just after midnight, reports CBS News correspondent Allen Pizzey.
Knox was visibly distraught after the verdict, Pizzey reports. Knox began weeping and murmured, "No, no," then hugged one of her lawyers. Her family said they were disappointed.
There is an automatic appeal, but that process could take as long as two years, Pizzey said.
Minutes after the verdict, 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 often 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.
One of Knox's lawyers, Luciano Ghirga, was asked if she was desperate.
"Yes, I challenge anyone not to be," he replied.
A group of local youths who gathered outside the courthouse shouted insults and "assassin" at the Knox entourage as they walked in to hear the verdict.
Knox and Sollecito were charged with murder and sexual assault in the slaying of Kercher more than two years ago. All three were studying in Perugia in Italy's central Umbria region at the time.
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.
Kercher's body was found in a pool of blood with her throat slit on Nov. 2, 2007, in the bedroom of the house she shared with Knox. Prosecutors contended the 21-year-old Leeds University student was murdered the previous night.
Maresca acknowledged that the defendants' loved ones were also pained.
"There is deep suffering on all sides," Maresca said, adding that the victim's family planned to hold a news conference late on Saturday.
Knox and Sollecito had been jailed since shortly after the slaying.
Relatives and friends in Seattle clasped hands as they watched TV and waited for the verdict. Her uncle, Mick Huff, cried, "Oh God, no" 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 university, said: "They're convicting a made-up person," Paxton said. "They they're convicting 'foxy Knoxy.' That's not Amanda."
The prosecutors contend 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."
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.
During the trial, 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.
Knox said Kercher was a friend whose slaying shocked and saddened her.
Defense lawyers have 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 say 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 maintains that a 6½-inch knife authorities found at Sollecito's house could be the murder weapon; they say Kercher's DNA was found on the blade and Knox's on the handle. However, defense lawyers argue 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.
Knox gave contradictory versions of the night of the slaying, saying at one point she was home and had to cover her ears to block out Kercher's screams and accusing a Congolese man of the killing. The man, Patrick Diya Lumumba, owns a pub in Perugia where Knox worked. He was jailed briefly but was later cleared and is seeking defamation damages from Knox.
Knox later contended that police pressure led her to initially accuse an innocent man.
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December 3, 2009 - Amanda Knox Pleads With Jury: I'm No "Assassin"
December 1, 2009 - Lawsuits Fly in Amanda Knox Murder Trial
November 24, 2009 - Amanda Knox: Sex-Game Murder Charge is "Pure Fantasy;" Italian Prosecutors Want Life Sentence
November 20, 2009 - Amanda Knox Trial: Convicted Killer Fingers Knox for Meredith Kercher Murder
June 19, 2009 - Knox's Mom Says Daughter, Victim Got Along
June 15, 2009 - "Always A Crescendo:" Amanda Knox Talks About Murder Investigation On Stand
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June 12, 2009 - Amanda Knox Finally Tells Her Side Of The Story
June 8, 2009 - Amanda Knox Set To Testify In Italian Murder Trial
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