Zuckerberg issued a public statement about the departure saying that he had enjoyed working with Systrom and Krieger.
Koum's departure in May followed the exit of his WhatsApp co-founder Brian Acton.
One of the names being touted as the next boss of Instagram is Adam Mosseri.
The people close to the matter have said that the co-founders didn't provide a reason for stepping down.
To lose one set of founders is unfortunate, but to lose the creators of a second billion-dollar business looks like carelessness on the part of Mark Zuckerberg, Facebook's chief executive. According to a report from Bloomberg, the two have lately become frustrated with "an uptick in day-to-day involvement from [Facebook CEO Mark] Zuckerberg, who has become more reliant on Instagram in planning for Facebook's future".
All of this said, hopefully Kevin and Mike's departure doesn't foreshadow an increasing Facebookification of Instagram.
"We're now ready for our next chapter", Systrom said in a blog post, speaking on behalf of Krieger and himself. He previously oversaw the Facebook's News Feed and Interfaces product management teams.
NOAA: Tropical Storm Kirk 2018 Projected Path, Spaghetti Models
As the storm moves away from the Cabo Verde Islands later Sunday, it was expected to have the opportunity to become a hurricane. While it has a chance to clip the Carolinas, the core of the system will stay off-shore as a frontal system over the U.S.
Alexis Sanchez will come good at Manchester United, insists teammate Paul Pogba
The 1-1 home draw with newly-promoted Wolves at the weekend saw £89m star Paul Pogba criticise Mourinho's tactics. And Pogba complained after the game that United's mistake was that they didn't attack more.
At UN, unrepentant Donald Trump set to rattle foes, friends alike
Moon's trip to NY is also aimed at explaining the outcome of his third bilateral summit with Kim to the world. Trump also says he's "excited" to be signing a new trade deal with South Korea.
In an interview with The Wall Street Journal that was conducted before Monday's announcement, Kevin makes clear he has no regrets about having sold Instagram to Facebook back in 2012.
Instagram is growing faster than Facebook's core app. In fact, it's already done this by adding tools like messaging, the ability to mute users and indications showing whether someone is online. This long ago stopped being an app that saw you fire it up, take a photo, slap on a filter, share some comments and likes and then were done with it.
"Instagram is the new Facebook, much more than it's the original Instagram", said a tweet from Benedict Evans, a venture investor with Andreessen Horowitz who blogs on the tech sector.
According to a Pew Research Center survey this year, 51 per cent of U.S. teens ages 13 to 17 use Facebook, compared with 72 per cent for Instagram and 69 per cent who are on Snapchat.
Instagram, meanwhile, has remained a bright spot for the company.
It's not an exaggeration to say that Instagram was the best acquisition in the technology industry for at least the last decade, and the founders were symbolically and pragmatically important to the most important growth asset that Facebook has right now. Facebook also saw the biggest single-day stock drop in history after its most recent earnings call in July.
Given Facebook's slowing growth and newer challenges, the company's leadership saw Instagram as the next obvious golden goose. "Instagram is the only platform that is growing". Instagram has been a bright spot for company not just because it's seen as a more uplifting place than Facebook itself, but because it is popular with teens and young people - a group Facebook has had trouble keeping around.
It was also ad-free.