The couple issued a joint statement confirming the split after spending 14 years together.
"Over the recent past, we have realized that our lives have gone in different directions and our romantic relationship has turned into a deep friendship," the couple said. "We will always be family and are fully supportive of each other and dedicated to the girls. Our personal lives remain personal and there will be no further comment."
Cuomo, 61, is serving his third term as New York's governor and Lee is a former host on the Food Network who has authored multiple bestselling cookbooks.
They have been together since meeting at a party in 2005, after Lee and her then-husband Bruce Karatz and Cuomo and his then-wife Kerry Kennedy, with whom he has three daughters, divorced.
Cuomo's sister, Margaret Cuomo, also issued a statement saying that Lee will remain "a sister and extraordinary friend" after the split.
"Sandy has always been a loving and generous presence in the lives of my three nieces and our entire family. We all love her dearly," she said.