The pair - played by Karen Gillan and Arthur Darvill - will depart the sci-fi drama in forthcoming mid-series finale 'The Angels Take Manhattan'.
"All stories have to end, and painful though that is, the most important thing about a story is how it finished," said Moffat. "I had over a year's warning to get this sorted out, and I'm very proud of what we've done. A fitting end to the mighty era of the Ponds!"
Head writer and showrunner Moffat explained that he had devised the characters' exit while in New York, which influenced the episode's setting.
"There was something about [returning monsters] the Weeping Angels and New York that just seemed to make sense to me," he revealed. "And I thought of the story for this episode while in New York.
"It's always good to find a new form for [the Angels] and we've got little cherubs this time. I had loads of ideas for the Weeping Angels on both the previous stories that I never got anywhere close to using, so it was good to find the opportunity."
Moffat previously revealed to Digital Spy that he "completely" rewrote Amy and Rory's final scenes after completing his first draft.
"I completely changed the ending as I was writing it, thinking 'No, I've got it wrong... I'm on the wrong emphasis' - but it's a good one and it's properly emotional," he insisted.
Doctor Who continues this Saturday (September 22) on BBC One and BBC America.