Born in Highland Park, Illinois, Cassidy is a graduate of Louisiana State University (LSU) and LSU School of Medicine. A gastroenterologist, he was elected to the Louisiana State Senate from the 16th district which included parts of Baton Rouge, in 2006. In 2008, he was elected as the U.S. Representative for Louisiana's 6th congressional district, defeating Democratic incumbent Don Cazayoux. In 2014, Cassidy defeated Democratic incumbent Mary Landrieu to represent Louisiana in the U.S. Senate, becoming the first Republican to hold the seat since Reconstruction. He was reelected in 2020.