After Birth is the story of a young woman named Ari who lives with her husband, Paul, in an abandoned mill town in upstate New York. They moved there after Paul got a job teaching in a local college. They bought a huge old house with lots of character and in need of regular repair. The town is economically depressed but Ari enjoys the antique shops, coffee shops and other entrepreneurial businesses she finds.

As the story opens, Ari and Paul's son, Walker, is a year old and Ari still suffers from postpartum depression from which she finds no relief until she befriends recent resident, Mina Morris. Mina is a poet and former member of a girl group with a very colorful past. Ari wants more than anything to make friends with the elusive Mina, who she thinks has to be more interesting than any of the other people Ari has found in town. Paul is a college professor, loyal husband and devoted father but he is not emotionally equipped to help Ari in her depressed state. Ari relies on wine and marijuana, given to her by her gay neighbors, Crispin and Jerry, to get her over the really bad parts in her life. When Ari needs a life line, Crispin and Jerry feed her dinners and let her spend hours of time at their house, just talking and laughing.

Ari has flashbacks of her life throughout the book which help fill in her life story so far. Ari's mother died from cancer when Ari was young, most probably having inherited the tendency from her own mother who took a synthetic hormone called DES to prevent miscarriages. Ari's story also includes her Jewish heritage including her maternal grandmother who survived the Auschwitz concentration camp by becoming a whore for Nazi soldiers. Ari's father and his new wife don't fully condone Ari's marriage to a man who isn't Jewish and can't get over the fact that Walker isn't circumcised.

When Mina has her own baby, Ari is finally able to bond with someone who has shared some of the same experiences. Ari has lacked the usual female support that most women receive after childbirth because she has no sisters and her mother died when she was young. Overall, Ari is angry about what has happened to her body as a result of a C-section and the unrelenting needs of her son. When Mina makes the decision to move back to the city, Ari is bereft but realizes that this is just another phase and she will build her new life with her husband and child the best she can.