Most attacks with unmanned aerial vehicles have been by the United States. Britain and Israel have also used them, and dozens more states are believed to possess the technology.
"The plain fact is that this technology is here to stay, and its use in theaters of conflict is a reality with which the world must contend," said inquiry leader Ben Emmerson, the U.N. special rapporteur on counter-terrorism and human rights.
"It is therefore imperative that appropriate legal and operational structures are urgently put in place to regulate its use in a manner that complies with the requirements of international law."
Criticism of drone strikes centers on the number of civilians killed and the fact that they are launched across sovereign states' borders so frequently - far more than conventional attacks by piloted aircraft.
Retired U.S. General Stanley McChrystal, who authored the U.S. counter-insurgency strategy in Afghanistan, warned earlier this month against overusing drones, which have provoked angry demonstrations in Pakistan.
Data collected by the Bureau of Investigative Journalism say 2,600-3,404 Pakistanis have been killed by drones, of which 473-889 were reported to be civilians.
The U.N.'s Human Rights Council asked Emmerson to start an investigation following requests by countries including Pakistan, Russia and China to look into drone attacks.
The inquiry will examine photographic and forensic material as well as witness statements. The resulting report and recommendations will be presented at the U.N. General Assembly in New York in October this year, Emmerson said.
He said that it he did not expect the inquiry to result in a "dossier of evidence" that would directly point to legal liability, but would help support the relevant states' own independent investigations.
Emmerson said Britain's Ministry of Defense had agreed to fully cooperate and he was optimistic he would receive good cooperation from the U.S. and Pakistani governments.
"We welcome this investigation in the hopes that global pressure will bring the U.S. back into line with international law requirements that strictly limit the use of lethal force," said Hina Shamsi, director of the American Civil Liberties Union's National Security Project.
"To date, there has been an abysmal lack of transparency and no accountability for the U.S. government's ever-expanding targeted killing program," she said.