Edward Sander Connolly, Jr. was born in San Francisco in 1965, the oldest of six children. He was raised in New Orleans, where his father was the chairman of the department of neurosurgery at the Ochsner Clinic. He attended the Isidore Newman School, Dartmouth College, and Louisiana State University School of Medicine, from which he graduated AOA in 1991. He completed his surgical internship at Columbia-Presbyterian Medical Center and a residency in neurological surgery at the New York Neurological Institute under Bennett Stein. In 1997, he joined the faculty as assistant professor of neurological surgery, director of the cerebrovascular research laboratory, and co-director of the neuro-ICU. He was named the Bennett M. Stein Professor of neurological surgery in 2008.

His clinical practice focuses on the microsurgical treatment of patients with cerebral aneurysms, arteriovenous malformations, carotid stenosis, moyamoya, as well as, cerebral hemorrhage and ischemia. His basic research interests span the spectrum of cerebrovascular disease with a focus on the role inflammatory cascades play in the pathophysiology of cerebral ischemia and cerebral hemorrhage. His clinical research efforts have been directed at improving the functional outcome of patients with cerebrovascular emergencies, as well as, the cognitive outcome of patients undergoing cerebral revascularization. In addition, he has worked collaboratively on the genetics of familial cerebral aneurysms. He serves on the executive committee of the AANS/CNS Joint Section for Cerebrovascular Surgery and the Society of University Neurosurgeons. He is on the editorial board of Neurosurgery, is editor-in-chief of Operative Neurosurgery, and has served the AANS as scientific program chair and annual meeting chair.

He and his wife Christine live in Greenwich Village and Springs, NY with their son, Jack.