CEO Kevin Systrom said they were departing to “explore our curiosity and creativity again”.
Instagram was purchased by Facebook in 2012 for $1 billion in cash and stock and has more than one billion users.
There had been reports of tension between the pair and Facebook, and the departures add to what has been a troubling year for the parent company.
Kevin Systrom, 34, and Mike Krieger, 32, the chief technical officer, started the image sharing site in 2010, and continued to run the service after it was acquired by Facebook.
They reportedly only told the Facebook leadership on September 24 so the departure appears pretty sudden.
Kevin Systrom said in a blog post: “We’re now ready for our next chapter.
“Building new things requires that we step back, understand what inspires us and match that with what the world needs; that’s what we plan to do.”
There was no animosity in the blog post. Kevin Systrom said the pair both remained “excited for the future of Instagram and Facebook”.
Facebook CEO Mark Zuckerberg said in a statement that Instagram reflected the founders’ “combined creative talents”.
“I’ve learned a lot working with them for the past six years and have really enjoyed it,” he said. “I’m looking forward to seeing what they build next.”
There have been reports of tension with Facebook’s leadership. Instagram’s popularity has soared in a period where use of the core Facebook product has stagnated.
This has put increased pressure on Facebook to squeeze more and more money from its users by adding new features some felt went against the Instagram app’s original focus on simplicity.
The latest Instagram product, IGTV, which allows posting of longer videos, in part to compete with YouTube, has not had an auspicious start. It was criticized this month after suggestive videos of children were recommended to its users.
Facebook has also been under intense pressure this year over the issues of safeguarding customer data and the misuse of its platforms by those wishing to spread fake news, including for political ends.
This, along with increased pressure from competitor platforms, appears to have led Mark Zuckerberg and his core executives to exert more control.
It ran counter to the business model the pair had become used to. Kevin Systrom had earlier praised the “tremendous freedom” Mark Zuckerberg had allowed since the takeover.
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