Her Italian ex-boyfriend Raffaele Sollecito was also convicted and sentenced to 25 years, the Italian news agency ANSA reported.
The Florence appeals court banned Sollecito from leaving Italy and ordered his passport confiscated.
Knox, who watched the proceedings from her Seattle home, said she was "frightened and saddened by this unjust verdict," ANSA reported.
"Having been found innocent before, I expected better from the Italian justice system," she said in a statement. "My family and I have suffered greatly from this wrongful persecution. ...
"This has gotten out of hand."
Knox said the verdict was "no consolation" to the Kercher family and called the prosecution "overzealous and intransigent," the investigation "prejudiced and narrow-minded" and accused Italian authorities of being unwilling to admit mistakes, instead relying on "unreliable testimony and evidence, character assassination, inconsistent and unfounded accusatory theory."
It was fourth ruling in the case, which is now expected to go to the Italian supreme court.
"Nothing will ever take away the experience of being wrongfully imprisoned," Knox, 26, told the New York Times in a Skype interview prior to the verdict, explaining why she exercised her right not to attend any part of the latest trial in the long-running legal saga.
"It remains that I would be putting myself in the hands of people who very clearly want me in prison for something that I didn't do," she said. "And I can't do that. I just can't. No. No way, no how."
She said she'd become such a known figure that her lawyers advised her to stay away.
"They said, 'If you go to the court, they're going to be paying attention to you -- they're going to be looking at your face, they're going to be trying to read your gestures, they're not going to be listening, and that is a huge problem,'" Knox told the newspaper.
She and Sollecito were arrested in 2007 for their role in what prosecutors described as a drug-fueled sex game that spiraled out of control.
The body of Kercher, 21, a foreign exchange student like Knox, was found on her bedroom floor in a pool of blood in the apartment she shared with Knox and others. Kercher had stab wounds to the throat.
Knox and Sollecito were convicted of sexual assault and murder in December 2009 and sentenced to 26 and 25 years, respectively. Their convictions were overturned on appeal in October 2011 by a panel of six jurors and two judges -- but the acquittals were overturned in March 2013 by the Court of Cassation, Italy's highest court, which ordered a new trial.
That trial, in Florence, started in the fall.
Another man, Rudy Guede, was convicted in a separate trial and sentenced to 16 years in prison.
Guede, who fled Italy after the murder and was later extradited from Germany, has admitted he was in Kercher's room that night but denies he killed her.
Defense lawyers argue he was the only one who committed the crime.
Prosecutors say the number and type of wounds to Kercher's body could not have been made by just one person.
Sollecito was present for some of the proceedings but was not there for the verdict, ANSA said.
Prosecutors had asked for Knox to be given a 30-year jail sentence -- four more years than her original sentence.
They asked for a 26-year term for Sollecito -- one year more than his first sentence.
Knox will have the opportunity to appeal at least one more time, her lawyer, Carlo Dalla Vedova, told the Wall Street Journal.
If she loses all appeals, Italy could seek her extradition.
It was unclear whether the United States would agree to send Knox back to Italy. One issue in the decision involves the interpretation of double jeopardy, the U.S. legal principle in which a suspect can't be tried twice for the same crime, legal experts told the Journal.
ANSA said Kercher's brother Kyle and sister Stephanie shook hands with lawyers after the verdict but otherwise showed no other emotion.