Former Wolves manager Mark McGhee will take over until the end of the season.
He replaces Jamie Howell who lost his job over the weekend.
McGhee also managed Reading, Brighton, Leicester City, Millwall, Motherwell, Aberdeen, Bristol Rovers and Barnet.
The experienced Scot said: “I live in Brighton, and when the call came to ask if I could assist at Eastbourne Borough I was delighted to offer my services.”
"I look forward to the challenge of helping to improve what is clearly a progressive club trying to do things the right way.”
Eastbourne parted with Howell after their 2-0 loss to Billericay.
“We can confirm the appointment of Mark McGhee as interim manager for the remainder of the season,” the club announced.
“Mark will be assisted by Danny Bloor, who remains at Priory Lane with Goalkeeper Coach Dean Lightwood.
“Welcome to Priory Lane, Mark!”