Born to a Dutch father and a British mother. She was named after her Dutch aunt, 'Jacoba', for which she developed the nickname 'Cobie.'

As a child Smulders wanted to be either a doctor or a marine biologist but started to gain an interest in acting in high school, appearing in several school productions. Discovered by a modeling agency in her teens, she started to model internationally, including in locations such as Paris, Japan, Milan, Greece, and Germany.

She finished high school in 2000 with high honors, being voted "Most Respected," and continued modeling for a few years before settling in Los Angeles to pursue an acting career.

She can speak French fluently, and currently resides in Los Angeles, California.