"It will have a tragic effect and disrupt government" Morgenthau said at a New York Press Club event.
"We will have 110,000 cases a year that will be in jeopardy," he said. Morgenthau served as Manhattan D.A. for 35 years before stepping down this year.
His comments come days after President Barack Obama said he has "not ruled out" holding the trials just blocks from where the Twin Towers fell in lower Manhattan.
"I think it's important for us to take into account the practical, logistical issues involved," he added.
"If you've got a city that is saying 'no' and a police department that's saying 'no' and a mayor that's saying 'no,' that makes it difficult," President Obama said.
Mayor Michael Bloomberg originally said he supported the plan, but when costs for security reached an estimated $1 billion, he said holding the trials elsewhere -- like a military base -- would make more sense. Police Commissioner Ray Kelly said he was never briefed by the Justice Department about its plans to stage the trials in lower Manhattan.
Morgenthau isn't the only one who thinks the trials should be held elsewhere.
A Quinnipiac University national poll of 2,617 registered voters found that the majority agrees that the trials should held outside of New York.
These voters prefer by a 56-35 percent margin that terrorism suspects be tried in military courts rather than civilian courts.
"When it comes to how suspected terrorists should be treated by the American judicial system there is a significant gap between the American people and President Barack Obama," said Peter Brown, assistant director of the Quinnipiac University Polling Institute.
The Justice Department said it is looking at other locations for the trials following strong opposition from both city residents and politicians -- as well as soaring costs for security.