McDermott will take over for Jim Johnson, who is on an indefinite leave of absence from the team while he undergoes cancer treatment. He was diagnosed with skin cancer in January. Johnson has been Philadelphia's defensive coordinator since 1999.
McDermott, 35, is Johnson's longest tenured assistant. He joined the team in 1998 as a scouting administrative coordinator and most recently served as linebackers coach (2007) and secondary coach (2008).
Eagles Coach Andy Reid said the team's "thoughts and prayers are with Jim Johnson and his family.
"As far as Sean McDermott, we have full confidence he can continue to lead this defense in his new role," Reid added. "He showed great command and presence in the offseason camps and has had an opportunity to learn from the best in the business. He's very smart, works very hard, and has a good rapport with the players and the assistant coaches. He's ready for this and I'm confident he'll do a great job."