The 52-year-old actress and 62-year-old musician were together for three years, and reportedly separated due to the strain of a long-distance relationship.
"It was the distance," a source told People. "She lives in New York and he resides in Indiana. It was the long distance that ultimately was the cause."
Mellencamp had expressed his reluctance to live in New York City to Rolling Stone in December.
"I'm too sensitive to live there," he shared. "I can't see poor people. I can't see the suffering. I can't see the trash on the streets." The singer mentioned he doesn't like Ryan being subjected to paparazzi attention, and declared, "I'm not leaving Indiana. I'm going to die here."
Mellencamp will release his 22nd studio album, Plain Spoken, in November. Ryan will narrate How I Met Your Mother spinoff How I Met Your Dad, and is scheduled for Ithaca in 2015.