Named for a brook that flowed through the area's farmland, Willowbrook once lay at the heart of the island's agricultural zone, and first saw other significant development when a military hospital opened there during World War II. After the war ended the property became the site of Willowbrook State School, a state-run institution for intellectually disabled children that became the scene of a national scandal in the 1970s when it was revealed that the children housed there were the victims of widespread abuse and neglect. The facility was forced to close by 1987, and six years later a campus of the College of Staten Island opened at the site. Willowbrook Park, a large city park, borders the college on the west. It was also home to the Seaview Hospital tuberculosis sanatorium, added to the National Register of Historic Places in 2005.

The neighborhood was also drastically transformed with the opening of the Verrazano-Narrows Bridge in November 1964. Soon after this, the farms were sold and broken up, and residential housing was built on the property. Many of the owners of the newly built homes were Jewish families, and as a result, Willowbrook became the center of the island's Orthodox Jewish community, which from the turn of the 20th century until the late 1960s and early 1970s was primarily centered in Staten Island's North Shore neighborhood of Tompkinsville along with most of Staten Island's then-small Jewish population.

The 2010s saw a great influx to the Jewish community in Willowbrook, because of the housing crisis in Brooklyn.