The scandal led Murdoch to shut down the 168-year-old tabloid and spurred criminal investigations in which dozens of journalists and officials have been arrested.
The jury also found former News of the World managing editor Stuart Kuttner not guilty of phone hacking.
Three other defendants Brooks' husband Charles, her former secretary Cheryl Carter and News International security chief Mark Hanna were acquitted of perverting the course of justice by attempting to hide evidence from police.
The defendants stood silently in the dock as the forewoman of the 11-member jury announced the verdicts.
Coulson showed no emotion as he was declared guilty. He faces a maximum sentence of two years in jail on the hacking conviction.
Brooks mouthed "thank you" after she was cleared of all charges, and exchanged a glance with Carter, standing next to her in the dock. After the verdicts she and her husband left court without speaking to reporters.
The jury, which has been deliberating for eight days, is still considering two charges of paying officials for royal phone directories against Coulson and former News of the World royal editor Clive Goodman.
Brooks and Coulson, both 46, were accused of conspiring, along with Kuttner, to hack phones between 2000 and 2006. She edited the News of the World from 2000 to 2003 with Coulson as her deputy and, the trial revealed, on-off lover. Coulson then took over as editor, before becoming Cameron's communications chief.
All the defendants denied wrongdoing. Prosecutors argued that senior editors must have known that hacking was taking place at the News of the World but only Coulson was convicted by the jury.
The verdict puts pressure on Cameron, who employed Coulson after two News of the World employees were convicted of phone hacking in 2007. Coulson quit Downing St. in 2011 when police re-opened their hacking investigation.
Cameron on Tuesday apologized for hiring Coulson.
"It was the wrong decision and I am very clear about that," he said.
Murdoch's British newspaper division, News U.K., said in a statement that it had already admitted and apologized for wrongdoing.
"We have been paying compensation to those affected and have cooperated with investigations," it said.
"We made changes in the way we do business to help ensure wrongdoing like this does not occur again."
It is the now-vindicated Brooks who has been the focus of most attention in what one lawyer called the "trial of the century." The case drew intense media and public interest from around the world. Brooks, in particular has been the subject of a level of media fascination and online abuse that her lawyer called a "witch hunt."
From humble origins in northern England, Brooks rose to become chief executive of Murdoch's influential British newspaper division and was a friend and neighbor of the prime minister as part of the horse-riding "Chipping Norton set," a reference to the tony rural town near her home. Friends included Cameron and former Prime Minister Tony Blair, who offered advice as the scandal erupted: "It will pass. Tough up."
Since the trial began at London's Central Criminal Court in October, the jury of eight women and three men has heard from police officers and royal functionaries, actors Jude Law and Sienna Miller, and the defendants themselves. In sometimes emotional testimony, Brooks described her "car crash" personal life, including a long affair with Coulson when both of them were married to other people.
Both prosecution and defense accepted that the News of the World hacked phones on a substantial scale. Intercepting voicemails was a specialty of private investigator Glenn Mulcaire, who was retained by the newspaper for almost 100,000 pounds (now about $168,000) a year. He was briefly jailed in 2007, along with royal editor Goodman, for hacking the phones of royal aides.
For several years Murdoch's company maintained the wrongdoing had been confined to Goodman and Mulcaire. That "rogue reporter" claim began to unravel in 2011, when The Guardian newspaper revealed that the News of the World had intercepted the voicemails of Milly Dowler, a 13-year-old girl who was kidnapped and murdered in 2002.
In the furor that followed, Murdoch shut down the paper and police relaunched criminal investigations into tabloid wrongdoing.
Dozens of journalists and officials have been arrested, and several former News of the World reporters and editors have pleaded guilty to hacking. Murdoch's News Corp. has paid millions in compensation to hacking victims.