Just two weeks after voters re-elected him to a ninth full term, Jackson sent his resignation letter to House Speaker John Boehner, citing his ongoing treatment for bipolar disorder and admitting "my share of mistakes."
The House Ethics Committee is investigating his dealings with imprisoned ex-Illinois Gov. Rod Blagojevich, and for the first time Jackson publicly acknowledged reports of a new federal probe believed to be looking into his possible misuse of campaign money.
"I am aware of the ongoing federal investigation into my activities and I am doing my best to address the situation responsibly, cooperate with the investigators, and accept responsibility for my mistakes," he wrote, adding "they are my mistakes and mine alone."
Jackson, 47, disappeared in June, and it was later revealed that he was being treated at the Mayo Clinic for bipolar disorder and gastrointestinal issues. He returned to his Washington home in September but went back to the clinic the next month, with his father, the Rev. Jesse Jackson, saying his son had not yet "regained his balance."
Attempts by The Associated Press to locate Jackson were unsuccessful Wednesday, and family members either declined to comment or could not be reached.
Jackson first took office in 1995 after winning a special election in a largely urban and Democratic district and began his career in Washington with a star power and pedigree that set him apart from his hundreds of other House colleagues.
But despite high expectations, he largely went unnoticed as a policymaker. Instead, he gained a reputation for quixotic pursuits such as trying to impeach President George W. Bush and push through constitutional amendments that had no chance.
He attended an elite private school in Washington and earned a law degree and a master's in theology. Over the years he bragged about spending his 21st birthday in jail after being arrested in an anti-apartheid protest, co-authored books with his father and developed his own a charismatic speaking style, with near perfect diction and often punctuated by finger pointing.
Shortly after taking office, he was deemed People magazine's Sexiest Politician in 1997 and became one of the most outspoken and most quoted liberals in the House. There was a near- Hollywood buzz over his svelte new figure in 2005 when he quietly dropped 50 pounds, disclosing months later that he had had weight-loss surgery.
Perhaps his shining moment as a Democratic leader was in 2008, when Jackson served as the national co-chair of Barack Obama's presidential campaign. He had his sights set on U.S. senator or Chicago's mayor.
Then came Blagojevich.
Though never charged, Jackson had to repeatedly dodge allegations that he was involved in discussions about raising campaign funds for the now-imprisoned former governor in exchange for an appointment to Obama's vacated U.S. Senate seat.
Jackson - who testified at Blagojevich's second corruption trial - always maintained that he was innocent and that his name would be cleared. Though through the proceedings it was revealed that Jackson had an extramarital affair, something his wife detailed in a front-page newspaper interview.
The congressman kept a low profile for years, avoiding interview requests and avoiding public appearances.
It wasn't until this year that glimpses of Jackson's former self emerged. He was forced to campaign seriously for the first time in years when former Rep. Debbie Halvorson put up an intense primary challenge. He easily won and gave a triumphant victory speech with his wife and children by his side.