The charges against Chaka Fattah, who represents Pennsylvania, include bribery, fraud and money laundering.
In one case, he is said to have used cash raised for an election campaign to pay off some of his son's student debt.
Mr Fattah, 58, who was first elected in 1994, is one of the most senior black lawmakers in Congress.
US prosecutors said four associates of Mr Fattah had also been charged.
They said the charges covered several schemes, including one in which he used federal grants and donations to his educational foundation to pay back part of a wealthy campaign supporter's $1 million (Â£640,000) loan.
He is also accused of disguising a lobbyist's bribe as payment for a car he never sold.
"The public does not expect their elected officials to misuse campaign funds, misappropriate government funds, accept bribes or commit bank fraud," US prosecutor Zane Memeger said.
"These types of criminal acts betray the public trust and undermine faith in government," Mr Memeger added.
Mr Fattah is yet to comment on the charges. His office said it would issue a statement later on Wednesday.
The 58-year-old remains free pending a yet-unscheduled court date.
House Democratic leader Nancy Pelosi said the charges against Mr Fattah were "deeply saddening" and that the congressman had a record of "distinguished service" in Congress.
She said he had "rightly" stepped down from his position as the top Democrat on the House subcommittee that oversees justice department spending.
Mr Fattah's son, Chaka Fattah Jr, was charged with fraud last year related to loans associated with a business he ran and is awaiting trial.
A veteran US Democratic congressman has been charged with misusing hundreds of thousands of dollars of federal, charitable and campaign funds.