The Ethiopian Airlines flight took off Saturday, headed on a two-hour journey from Addis Abbaba to Nairobi.
"I am very happy to see the airplane is back to the air now, and I am very happy also we are the first one," Ethiopian Airlines CEO Tewolde Gebremariam told journalists before takeoff.
The aircraft will return to the Ethiopian capital later in the day, airline officials said.
Regulators grounded the Dreamliner worldwide on January 16 after problems with the lithium-ion battery on the aircraft. One plane's battery caught fire on the ground at Boston's Logan International Airport, while another 787 was forced into an emergency landing in Japan after the battery overheated. The cause of these problems has not been identified.
On Thursday, the US Federal Aviation Administration approved a new battery design, clearing the way for international carriers to resume 787 flights after months of investigation. Japanese regulators gave the all-clear on Friday.
Japanese airline to resume tests
On Sunday, Japan's All Nippon Airways (ANA) will begin testing one of its modified Dreamliner jets.
Speaking to reporters in Tokyo on Saturday, Boeing's chief engineer for the 787 said that the new battery system is designed to prevent a fire and contain one should it occur within an "enclosure," which is a special casing that surrounds the battery to prevent heat from being released in the aircraft.
"Even if we never know root cause, the enclosure keeps the airplane safe, it eliminates the possibility of fire, it keeps heat out of the airplane, it keeps smoke out of the airplane, and it ensures that no matter what happens to the battery, regardless of root cause, the airplane is safe," he said, adding that "in some ways it almost doesn't matter what the root cause was."
ANA Chairman Shinchiro Ito will be aboard Sunday's test flight, which will begin and end at Toyko's Haneda airport.
"While we deeply regret the impact this has had to our customers and to the flying public, especially here in Japan where so many of these airplanes are operated, we believe our solution is comprehensive and we know that our airplane is safe," said Sinnett.
Japan's two biggest carriers, ANA and Japan Airlines, have the most 787s – 17 and seven, respectively. They began new battery installations last week and company officials have said commercial flights would resume in June.
dr/mkg (AFP, AP, Reuters, dpa)