Natalie Marino has made a career writing about happily-ever-afters, making her own life an open book in order to help others. She never expected her husband, to come home one day and demand a divorce so he can be with his pregnant mistress. To Natalie, who's struggled with infertility, it's the worst betrayal imaginable. She's still dealing with the shock when her father calls, delivering another blow: Her mother's Alzheimer's has progressed. He wants Natalie and her sister to come home while she can still recognize them.

Desperate for a change of scenery, Natalie decides a road trip is in order, even if her estranged sister isn't the most obvious travelling companion. She and Lindsay will take Route 66 – the mother road – from Santa Monica, California, to their childhood home in Illinois. But when she picks up her sister, she's in for another shock: Lindsay is pregnant.

In a road trip that's one part Lucy and Ethel, one part Thelma and Louise, the two sisters trade snarky barbs, visit quirky tourists spots, and dodge Ben, Lindsay's ex-boyfriend turned stalker. Will their trip down the mother road bring the two sisters closer together, or turn out to be the biggest wrong turn yet?