Blagojevich was indicted on charges of racketeering conspiracy, wire fraud, extortion conspiracy and attempted extortion, and making false statements.
Most of those charges carry a maximum sentence of 20 years in prison and a $250,000 fine.
The wide-ranging charges say Blagojevich allegedly traded official duties for money and employment beyond his term of office.
The indictment returned Thursday paints Blagojevich as intent on grinding out as much campaign cash as possible and filling his pockets - even if it meant committing extortion and fraud.
The refinancing of billions of dollars in state pension money was in play in a massive kickback scheme, the indictment says. It says his wife got thousands of dollars in unearned real estate fees and a $12,000-a-month spot on convicted fixer Tony Rezko's payroll.
The indictment also alleges the ousted governor hoped to get a lofty Cabinet post, substantial campaign cash or a high-paying job for his wife in exchange for filling the vacant Senate seat of Barack Obama.
CBS News correspondent Dean Reynolds reports that 16 of the 19 felony counts in the new indictment involve Blagojevich himself, though also named were:
"We were hoping that it wouldn't happen but now we go to trial and win," Robert Blagojevich's attorney, Michael Ettinger, said after the indictment.
The then-governor was arrested Dec. 9 on a criminal complaint and U.S. Attorney Patrick J. Fitzgerald faced a Tuesday deadline to supplant it with an indictment handed up by a federal grand jury.
Blagojevich, 52, who was impeached in January after the scandal boiled over, always maintained he is innocent.
"I am not guilty of any criminal wrongdoing," he has said.
Since the governor's arrest in December, he has been a frequent presence on the talk show circuit. He's even hosted his own local radio show on which he claimed, "I was hijacked from office."
But on the day of his indictment, the usually high-profile former governor was secluded at Disney World in Florida.
"I'm saddened and hurt but I am not surprised by the indictment," he said in a statement. "I am innocent. I now will fight in the courts to clear my name."
The Democrat's arrest led to his political downfall: The Illinois House impeached him Jan. 9. The Senate convicted him and removed him from office Jan. 29.
Illinois political figures chimed in on the indictment.
"There is a serious crisis of integrity in our government," said Gov. Pat Quinn. "And I think it's very important that we the people confront this crisis in active reforms that will solve the problems and make sure that they won't happen again."
Rep. Mark Kirk, R-Ill., said, "It's a stunning indictment not just of the governor but his family and all of his closest associates. Three hundred and fifty years in jail. But I think it's a welcomed development to end a culture of corruption which is throughout the state of Illinois."
Former Illinois Attorney General Roland Burris, who was named by Blagojevich to fill Obama's Senate seat, would not comment on the indictment, according to spokesman Jim O'Connor. Earlier in the day, Burris told reporters with The Hill as he came off the Senate floor that it "has nothing to do with me."
Meanwhile, Illinois residents expressed corruption fatigue Thursday.
"I'm so disgusted," said Linda Dowdy, a 59-year-old Belleville tavern manager who calls herself a hardcore Democrat. She lamented even well-intentioned politicians don't last long in office.
"He may have every intention of going in and trying to change things and of making things better," she said. "But once he's in, he doesn't have any choice but to be as crooked as they are or he's not gonna stay in there."
Squeezing Hospital Owners, Lining Pockets
Prosecutors accuse Blagojevich and members of his inner circle of scheming to line their pockets with millions of dollars squeezed out of contractors, hospital owners and others seeking state business and then planning to divide up the proceeds after he left office.
In one incident, the indictment says an Illinois congressman asked about a $2 million grant included in the state budget for a school. But Blagojevich allegedly told a state official to tell the lawmaker his brother would have to raise campaign funds or the grant wouldn't go through.
That congressman is now Obama's chief of staff, Rahm Emanuel, attorneys familiar with the case said. They spoke on condition of anonymity because the congressman isn't named in the indictment and the information is secret grand jury material.
At the time, Emanuel represented the 5th District on Chicago's North Side. Some of the funds were later released, even though no fundraiser had been held.
The indictment does not say which of Emanuel's two brothers was involved. Emanuel's brother Ari is a Hollywood agent and the inspiration for Ari Gold, the Type-A superagent on the HBO series "Entourage." His brother Ezekiel is an oncologist.
President Obama's deputy press secretary, Josh Earnest, said the White House would not comment on the indictment, which does not allege wrongdoing by Mr. Obama or his aides.
The indictment also accuses Blagojevich of seeking to withhold state aid from Tribune Co. unless it fired Chicago Tribune editorial writers urging his impeachment.
And, prosecutors claim Blagojevich told an aide he didn't want executives with two financial institutions getting further state business after he concluded they were not helping his wife get a high-paying job. She was not charged.
The indictment seeks to seize at least $188,370 held by the Friends of Blagojevich campaign fund. CBS Station WBBM reports that prosecutors are moving to seize the former governor's Chicago home, his Washington apartment, and the $3 million he planned to use to pay for his legal defense.