The ex-service chiefs claimed the UK would be in a “stronger” position to deal with the terror group, also known as Daesh, by staying in the EU.
The intervention by the former Royal Navy, Army and Royal Air Force officials comes four months ahead of a referendum of Britain”s links to Brussels.
This weekend David Cameron announced the in/out vote would be held on June 23 after agreeing a series of reforms with bureaucrats.
In a letter in part co-ordinated by Downing Street, the former commanders told of their concern about the rise of ISIS.
They said: “Europe today is facing a series of grave security challenges, from instability in the Middle East and the rise of Daesh, to resurgent Russian nationalism and aggression.
“Britain will have to confront these challenges whether it is inside or outside the EU. But within the EU, we are stronger.”
Signatories to the letter include former chiefs of defence staff Field Marshal Lord Bramall and Field Marshal Lord Guthrie.
Air Chief Marshal Lord Stirrup and Admiral of the Fleet Lord Boyce are also among the 13 senior officers who backed the letter.
Other supporters included former special forces chief General Sir Michael Rose, according to the Telegraph.
ISIS, which was behind the horrendous Paris attacks on November 13, has repeatedly threatened to target London.
Earlier this month the crazed militants released a chilling video featuring tourist hotspots in the capital – including Buckingham Palace, Big Ben and Tower Bridge.
The propaganda film also included a clip of David Cameron, who voted to authorise airstrikes against ISIS jihadists in Syria in December.