"Well, Chris, it does appear that it was an act of terrorism. Exactly how, of course, the investigation will have to determine," Clinton told CNN's Chris Cuomo in an interview.
Wreckage from the EgyptAir Flight 804 has been recovered near the Greek island Karpathos as Egyptian and Greek authorities on Thursday continued to investigate the crash.
Clinton made her comments as reports emerged that Egyptian officials suggested terrorism was a more likely cause than technical failure for the jet's downing in the Mediterranean.
Donald TrumpDonald John TrumpCorker: US must determine responsibility in Saudi journalist's death Five takeaways from testy Heller-Rosen debate in Nevada Dem senator calls for US action after 'preposterous' Saudi explanation MORE, the presumptive GOP presidential nominee, sent a tweet early Thursday morning in which he said the flight that disappeared from radar "looks like yet another terrorist attack."
Former Defense Secretary and CIA Director Robert Gates said later Thursday morning on MSNBC, "It's always better to wait until you actually know what the facts are before you open up.”
The White House indicated later in the day that it was too early to tell what happened to the Airbus A320 that went down with 66 passengers and crew on board.
Clinton's more cautious comments on the flight's downing came amid an interview where she slammed Trump for being a "loose cannon" on foreign policy.
Clinton said the jetliner incident "shines a very bright light on the threats that we face from organized terror groups," mentioning the Islamic State in Iraq and Syria (ISIS).
"ISIS, of course, but then there are other networks of terrorists that have to be hunted down and defeated," she said.
"I think it reinforces the need for American leadership, for the kind of smart, steady leadership that only America can provide in working with our allies, our partners, our friends in the Middle East and elsewhere," she said. 
Clinton also focused on the flight's origin from Europe, where she has pushed for greater anti-terrorism collaboration.
"Our biggest concern is what's going on in Europe, and that is something that we do have to address and deal with with all of our partners, and that's going to have to require closer cooperation," she said.