In a 2012 interview with Vice, Kirke said she met Michael Mosberg, a former lawyer, at a doctor's office when she had bronchitis. "I don't remember what he was there for, but I liked him and gave him my number. We've been together for four years and married for three of them," she said at the time. Years later, Kirke revealed in a 2016 interview with The Telegraph that she met Mosberg while in rehab when she was 23, but did not wish to discuss it before that point.
Regardless of how the two met, Kirke and Mosberg connected right away, and the two married in 2009, a year after they initially met. On being married at 24 years-old, Kirke told the Purple Magazine in 2012, "I finally wanted the experience of being happy, so I went off my blueprint, fell in love with a lawyer from Long Island, and then had a baby." Together, the couple share two children: Rafaella Israel (born 2010) and Memphis (born 2012).
The two remained together until their split in 2017 after seven years of marriage. Among many factors, Kirke revealed that communication and her acting career put a strain on their marriage. The actress told W Magazine in 2017, "I wish the conversation we had had gone, 'Yeah, I'm struggling in the marriage right now,' but I think it wasn't something we were able to face because again, the societal consensus is that everything has to be either good or bad, or right and wrong. But it's wrong to be married and be unhappy and stay." She also explained to The Evening Standard that acting forced her to look into her own life and find what she truly wanted.