During the hip-hop musical, centered on the life of Alexander Hamilton, the founding father's wife Eliza sings a love song titled "That Would Be Enough."
Miranda was one of the many guests to sit down with Winfrey at the live event, which will air on Feb. 27 at 10 p.m. ET/PT on OWN. It'll also be available on Oprah Winfrey's podcast of the same name.
"It's just a moment when Eliza is telling Hamilton, 'As long as you come home at the end of the day that would be enough,'" Manuel continued.
"My wife is gonna kill me for telling this story, she doesn't like how she comes off in this story," Manuel said before explaining.
Miranda said he eventually played the song for his wife, Vanessa Nadal.
"I played it for my wife; tears streaming down my cheeks. And she goes, 'Is that what you wish I would say to you?'" he said with a laugh. "And I'm like, 'No! That's my love song to you!'"
The two wed in 2010 and welcomed their first child, a son named Sebastian, four years later. They recently welcomed another son, Francisco, last week.
"You have this new person that with any luck is gonna get some of the attributes of the love of your life," the Tony Award-winning playwright and composer added. "It's wonderful."