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."