His departure is as a big of a surprise as his appointment was 10 years ago.
"I could just assure you that I will work as hard as I can to do the best job that I can," said Fitzgerald when appointed.
Fitzgerald's hard charging, no-nonsense style sent shivers through the spines of crooked politicians, mobsters and others involved in mischief.
He announced his resignation in a statement that reads, in part: "When I was selected for this position in 2001, I said that it was one of the greatest opportunities that one could ever hope for, and I believe that even more now after having the privilege of working alongside hundreds of dedicated prosecutors and agents. I have tried not to get in their way ... this was a great office when I arrived, and I have no doubt that it will continue to be a great office."
Fitzgerald doesn't give a reason for leaving. He says he doesn't have a job lined up and will take time off this summer before making any career decisions.
"He's an aggressive, hard working prosecutor," said said Ron Safer, former federal prosecutor, Schiff Hardin. "That was the tone he set, and that's what he got."
Two governors, several aldermen, a city clerk, a suburban mayor and organized crime figures all found themselves caught in Fitzergald's crosshairs and were convicted.
Criminal defense attorney Mike Monico represented former Rod Blagojevich confidant Chris Kelly, who committed suicide under the pressure of prosecution.
"His tactics are tough," said Monico. "They wanted Mr. Kelly to testify against the governor and he didn't want to. He paid a very, very stiff price for that."
As news spread around the federal courthouse Wednesday, many wonder what's next for Pat Fitzgerald.
"I don't know if I could afford him, but I would be more than happy to have come over to the dark side with us," said Joe Lopez, a criminal defense attorney who represents members of the Chicago Outfit.
Fitzgerald's name is frequently mentioned as a candidate for the job of FBI director. By tradition, it falls to Senator Dick Durbin to recommend Fitzgerald's replacement.
U.S. Sen. Dick Durbin praised Fitzgerald for his "aggressive prosecution of wrongdoing -- including politicians in both parties." Durbin adds that Fitzgerald "has given fair warning that no one is above the law."
Gov. Pat Quinn credited Fitzgerald for making Illinois "a more ethical state."
Fitzgerald will talk to reporters about his decision to resign at a news conference Thursday morning at 10:30 a.m.
Before coming to Chicago, Fitzgerald was an assistant U.S. attorney in New York.
Robert Blagojevich reacts
Rod Blagojevich's brother Robert accuses Fitzgerald of abusing his power by prosecuting the former governor.
"It was long overdue," Robert Blagojevich said. "He had been in office as a public servant for many years and amassed a lot of power, and I believe was allowed to overreach with his prosecution, and in my case, the agenda was to convict my brother."
Robert Blagojevich says fighting the federal government was a nightmare, and Fitzgerald did not use the law as it was meant to serve the public.
"There is no way the I would buy into that, sadly a myth to me, that this prosecutor and his office were about fairness and justice," he said.
Blagojevich also said the case against his younger brother was flawed and he has a strong case for an appeal for many reasons.
"Nearly 100 intercepts. My brother's team was only able to get in four or five," he said.
ABC7 asked Blagojevich if he has had any communication with his brother since Rod reported to prison or talked to Rod's wife or children.
"I've got no comment on my brother or family," Blagojevich said.
Blagojevich is still waiting to testify before the House ethics committee investigating Jesse Jackson Junior and his possible connection to the sale of President Obama's former U.S. Senate seat.
"The representatives that came to meet with an offer were representing Congressman Jesse Jackson Junior. I was approached by two individuals, one offering $1.5 million and another one offering $6 million, so that to me is a little bit frustrating knowing that this all went on and nothing has happened," he said.
Prosecutors have never accused Jackson of doing anything illegal and Jackson has long denied any wrongdoing.
Blagojevich is in town to speak to the Chicago Bar Association Thursday and he said he is going to begin his speech by telling the story of how the feds knocked on his door the morning of Dec. 9, 2008.