The 68-year-old Johnson took an indefinite leave of absence in May to continue treatment for a cancerous tumor on his spine. It's uncertain whether he'll return to the team in any capacity.
"First and foremost, our thoughts and prayers are with Jim Johnson and his family as they battle through this difficult time in his cancer treatments," Eagles coach Andy Reid said Friday. "I have been in constant communication with Jim and his wife throughout this offseason and they are thankful for all the support they have received from the Eagles organization, the fans and the entire NFL community."
McDermott, 35, will be introduced at a news conference Saturday afternoon. He ran the defense in Johnson's absence after serving as secondary coach last year.
McDermott originally joined the Eagles in 1998 as a scouting administrative coordinator, and has served in various roles as an assistant on the defensive staff.
"We have full confidence he can continue to lead this defense in his new role," Reid said. "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."
McDermott has big shoes to fill. Johnson is widely regarded as one of the top defensive masterminds in the game. He's known for his aggressive, attacking style and his defenses have played a major role in the team's success over the last decade.
"This will be a big test for all us," said cornerback Sheldon Brown, the lone remaining defensive starter from the Eagles' Super Bowl team in 2005. "It will be interesting to see how things go if we get off to a slow start defensively. That'll be the big test. Without Jim there, how do we react and re-group?"
Last year, the Eagles finished third in total defense and fourth in points allowed. They advanced to the NFC title game for the fifth time in 10 seasons.
Johnson spent two seasons in the NFL as a player with the Buffalo Bills in 1963 and 1964. He began his coaching career at Missouri Southern in 1967, and was the secondary coach at Notre Dame when the Fighting Irish won the national championship in 1977.
Johnson spent the last 23 seasons coaching in the NFL, including 10 years as Philadelphia's defensive coordinator.
"The thing about Jim was his ability to watch what was happening on the field and counter-punch," said former Eagles cornerback Lito Sheppard, who now plays for Jets coach Rex Ryan. "That takes knowledge and ability -- Sean has that. But it also takes instincts and experience. And you can only get that by doing it."
Information from ESPN reporter Sal Paolantonio and The Associated Press was used in this report.