In a joint statement, the Instagram founders said they were "ready for the next chapter" and "planning on taking some time off to explore our curiosity and creativity again".
Yet Zuckerberg's Facebook has to make sure it doesn't become akin to a swarm of locusts, moving from platform to platform and turning each one to a husk. "Now eight years we look back and are proud and grateful to have been part of that journey".
"Kevin and Mike are extraordinary product leaders and Instagram reflects their combined creative talents", Mark Zuckerberg wrote in a statement.
John Lilly, a venture capitalist at Greylock, commented on the departure of the two Instagram co-founders stating, "what an impact they've had on all of us".
Instagram Stories, which is one of the many attempts to clone rival Snapchat's disappearing videos feature, is now twice as big as Snap with more than 400 million daily users.
The two were inspired to create the Instagram app - originally launched just for iPhones in 2010 - by old Polaroid pictures.
Aaron Rodgers admits concern that knee injury will worsen
Jones, who showed flashes of potential as a rookie last season, can bring a slashing, physical presence to the backfield. For the second consecutive week, Clay Matthews was called for a controversial roughing the passer penalty.
Systrom's fortune is valued at $1.4 billion by Forbes. "California's economy is highly reliant on innovation and the bringing to market of new ideas". Bloomberg reports that the departure comes amid increasing friction between the pair and Facebook CEO Mark Zuckerberg.
Their sudden resignations came only months after Jan Koum and Brian Acton, the billionaire founders of Whatsapp, the messaging platform, resigned from Facebook. You could even argue that Instagram was positioned as an anti-Facebook, although there has been a notable creep of ads and Facebook-style branding in recent updates.
As such, he thinks Facebook would be wise to reassure users that what they love about Instagram isn't going to change - that they are not going to be forced to integrate with Facebook.
And eMarketer has estimated that Facebook would lose some two million United States users under age 24 this year.
Kevin Systrom and Mike Krieger were responsible for that culture - the entire feel of an app that was in many respects the anti-Facebook.
Facebook and other tech firms have been facing criticism from President Donald Trump and his allies, accusing Silicon Valley of bias against conservatives and warning of regulatory action.
Instagram has thus far been a bright spot in Facebook's portfolio, largely (though not entirely) untainted by controversies - but the cofounder team's departures raises questions about the direction and future of the wildly popular app.