The British actor-comedian filed the documents in Los Angeles, citing "irreconcilable differences", reports TMZ.
He announced: "Sadly, Katy and I are ending our marriage. I'll always adore her and I know we'll remain friends."
The news came after it was reported that the couple were "dealing with something" in their marriage.
Brand and Perry, who tied the knot in October 2010, recently spent Christmas 7,000 miles apart following an alleged "massive fight".
A source previously said: "She was like, 'F**k you. I'm going to do my own thing'. Russell replied, 'Fine, f**k you, too'... Things are not good. The fighting is getting worse."
Brand was later seen not wearing his wedding ring.
Both stars had up until now denied rumours of their separation.
Brand joked about the speculation: "There are always rumours, aren't there? In the end you have to just not engage with internet technology, which is difficult because a lot of the nude women websites I quite enjoy.
"I've treated the whole internet now like it's a wicked little liar. Yeah. I am really happily married. I'm married to Katy. Perpetually, until death do us part was the pledge."
Perry said earlier his month: "First I'm pregnant & then I'm divorced. What am I All My Children?! Erica Kane… pshhh… If I had a dollar for every time…"
Watch the video for Katy Perry's 'The One That Got Away' below: