They'd seized two knives in their search for a weapon. They took DNA from the room where Kercher was killed. And at least one suspect had confessed to being at the scene. Or so they said.
Kercher had been stabbed in a sexual misadventure, officials said. And they knew the killers.
Knox's photo was even hung in the police plaza alongside Italy's most infamous mobsters and criminals.
The prosecution case seemed a sensational slam-dunk, almost too good to be true.
Knox's supporters say that's because it is.
"In the beginning, all of this supposed evidence was being leaked, showing what sounded like a pretty convincing case," Anne Bremner, a lawyer and former prosecutor working with the group Friends of Amanda, told CNN.
The case couldn't look more different depending on where you stand.
That is as true now, as Knox and Sollecito await the decision of Italy's highest court
on whether to uphold their murder convictions.
Knox -- a 27-year-old native of Seattle, Washington -- and Sollecito were convicted in 2009 of the killing of Kercher. Sollecito and Knox were acquitted in 2011 on appeal, and then Knox returned to the United States.
Italy's Supreme Court decided in 2013 to retry the case, saying the jury that acquitted Knox and Sollecito didn't consider all the evidence, and that discrepancies in testimony needed to be answered.
In January 2014 the acquittals were overturned, and Knox was sentenced in absentia to 28½ years in prison. Sollecito was sentenced to 25 years.
Speaking on ABC's "Good Morning America,"
Knox said news of the guilty verdict "really has hit me like a train."
"I did not expect this to happen. I really expected so much better from the Italian justice system," she said. "They found me innocent before. How can they say that it's guilt beyond a reasonable doubt?
After the verdict, Italian authorities stopped Sollecito near the border with Austria and Slovenia, Italian police said.
Sollecito, who is not allowed to leave Italy while the legal process continues, was in the northern Italian town of Udine, police said. Sollecito's lawyer said his client never intended to flee the country, but he was driving with his girlfriend to her house in Udine when they were forced to stop due to snow.
Same evidence, two very different conclusions
The case has always been about the evidence. But how you view the evidence, simply depends on what side you believe. It all comes down to disputed DNA.
In Knox's corner: her friends and family from Seattle.
For them, she is the victim -- railroaded by an overzealous Italian prosecutor, whose credibility was marred by allegations of prosecutorial misconduct in another case.
Knox's supporters have said he tried to force the evidence to fit his theory of what happened. And with negative and often false details about the case appearing in the press -- all for the world to read -- Knox supporters feared she would be convicted regardless of the facts.
On the other side: Perugia's prosecutor Giuliano Mignini. For him and his colleagues, the answer is simple -- Guede, Knox and Sollecito are all responsible for leaving Kercher partially clothed, strangled and with her throat cut on November 2, 2007.
And the two sides still couldn't be further apart on how they view the very evidence that has over the course of nearly eight years both been used to find her guilty and to overturn that ruling.
Independent experts testified during the 2011 appeal that they believed some evidence had been contaminated.
The testimony fueled the fire that started during the first trial about the effectiveness of Italy's justice system given widespread doubts over the handling of the investigation and key pieces of evidence.
But Italian prosecutors, police and those who collected the evidence maintain those arguments are nothing more than last-ditch efforts by a pair guilty of murdering Kercher in cold blood.
And the second conviction shows the Italian court, this time, believes the prosecution. But questions about the specific pieces evidence that led to two convictions and one acquittal still continue.
The murder weapon: The knife
The crime scene was gruesome. The 21-year old British student was found under a duvet on the floor by her bed, covered in blood. A bloody handprint was streaked on the wall above her.
A source close to the prosecution says Kercher was held down while she was strangled and stabbed. The source says Sollecito's 6½-inch kitchen knife was used to slit her throat and then taken back to his apartment.
Knox's DNA is on the handle and that of Kercher is on the blade, said a source close to the prosecution who did not wish to be identified discussing an ongoing case.
Kercher had never been to Sollecito's apartment and wouldn't have come in contact with the knife, he said, yet there was her DNA. Those "unmistakable facts" show the knife played a role in the murder, the source said.
Bremner and experts testifying for the defense say there is no way that specific knife could be the murder weapon.
Dr. Carlo Torre, a leading forensics expert in Italy, testified that the knife taken from Sollecito's apartment wouldn't have made the wounds on Kercher's body.
"It doesn't match the size or shape (of the wounds)," Bremner told CNN. "And Sollecito's knife also doesn't match a bloody outline of a knife left on the bedding."
Bremner, who offered her legal advice pro bono to the Knox family, questioned the validity of the DNA evidence, saying the knife had been "improperly transported in a shoe box."
Furthermore, Bremner said the jury heard from defense expert Sarah Gino, a geneticist and private coroner in Italy, who said that the DNA sample was too small to be definitive. Bremner said the presence of Knox's DNA on the knife handle was no surprise, as the couple had dinner at Sollecito's house occasionally.
Prosecutors have maintained just because the knife doesn't match everything doesn't mean it wasn't used. The source close to the prosecution said it was possible, based on the wounds, that several items made them.
Damning DNA or 'Fellini Forensics'
On the night Kercher was killed, Knox and her boyfriend say they were at his house watching a movie and smoking hashish.
Their recollection of events, they admitted, was hazy from the drugs, but both swore they went back to the house the next morning. Knox says she was unable to gain entry -- and called police.
For their case, prosecutors had to prove that Knox and Sollecito -- who had recently started dating -- were lying and place them at the home when Kercher was killed.
Some reports spoke of a scurry of people -- more than one -- on the night of the murder around the house. It was a positive lead for prosecutor Mignini -- but came to nothing in court.
But the prosecution had more evidence in the form of a bra clasp, one that fell to the floor after the murderer cut Kercher's bra in half before she was killed.
And on it was Sollecito's DNA.
Bremner says that evidence on the clasp is fundamentally flawed, like much from the crime scene collection, calling the work "Fellini forensics."
"In the (crime scene) video, you can see it went from being white in color to nearly black because it got so dirty being moved around," Bremner said of the clasp, noting that tainted the only evidence that placed Sollecito at the scene.
Bremner described other errors she saw on the crime scene video.
"They were putting their fingers in Kercher's wound, they were shaking out evidence, picking up hairs and dropping them," she said. "Some people didn't wear gloves or had their hair draping on the floor, they crashed into a window at one point and threw aside evidence. It was just wrong on all levels."
The prosecution source maintains the crime scene was handled properly, and the evidence shows what it shows.
A big win for Italy or the 'greatest travesty' ever?
Knox's introduction to the world came in a whirlwind of tabloid headlines.
The prosecution touted hard evidence early that they said unquestionably showed they had their killers.
There was a footprint in Knox and Kercher's bathroom that was attributed to Sollecito -- though later analysts admitted it belonged to Guede, who was convicted of Kercher's murder in 2008.
The prosecution also presented what they called a confession by Knox, but she later said any apparent admission she was at the scene was made when investigators told her to imagine what she might have seen if she had been there.
The argument became moot when a higher court ruled the alleged confession could not be used because the statement was made without an attorney or translator present.
The tabloid headlines continue as Knox's third ruling was handed down and she was convicted for a second time.
Media around the world focused early on Knox's sexual history, what clothes she wore to court and whether a bump on her lip meant the girl they dubbed "Foxy Knoxy" has herpes.
From then on it has all been distraction from the lack of evidence, Bremner said.
"It's the greatest travesty of a prosecution ever," Bremner said. "It's so ludicrous. You've got to have a theory, or a motive, but the theory has to fit the facts somehow. And in this case, there's no solid evidence, no motive and no match whatsoever."
Knox's supporters maintain that the prosecution did get one thing right -- putting Guede behind bars. He chose a fast-track trial, separate from Sollecito and Knox. He was convicted of murder and attempted sexual assault and sentenced to 30 years. They believe he was Kercher's sole killer. He appealed the verdict, which was upheld, but his sentence was reduced to 16 years.
Supporters of Knox and Sollecito say they are only being prosecuted because the pair was flaunted so publicly as the killers for so long that it would look bad for officials to admit they got it wrong.
The prosecution source rejects that, and portrays Knox, Sollecito and Guede as three people who together ended the life of the young British woman. And they say the way Knox originally pointed the finger at another man -- who was cleared with an alibi -- shows she had something to hide.
Both sides agree the truth is in the evidence; the question is which truth reveals what really happened the night Kercher died. And the truth may be, we'll never know.