The exodus is bipartisan, with five Democrats leaving the 61-member committee while seven Republicans follow suit.
"This is a significant shift in terms of total number," said Isaac Boltansky, a policy analyst for Compass Point Trading & Research.
The biggest change for the panel will be in who heads it. The current chairman, Rep. Spencer Bachus, R-Ala., is widely anticipated to pass the gavel to Rep. Jeb Hensarling, R-Texas, due to term limits. And Rep. Maxine Waters, D-Calif., is expected to take over for retiring Rep. Barney Frank, D-Mass., as the panel's lead Democrat.
But many observers pointed to significant departures of senior members of the committee. In addition to Frank, Reps. Ron Paul, R-Texas, Gary Ackerman, D-N.Y., and Bradley Miller, D-Calif., are planning to retire, while Rep. Joe Donnelly, D-Ind., will be leaving the committee for the Senate.
Frank's departure is likely to impact the committee the most, given his deep knowledge of financial services issues and accessibility to bankers.
"Barney was a key leader on that committee even before he was chairman," said Dan Forte, president of the Massachusetts Bankers Association. "It's a significant loss for the country, for the industry and from a public policy standpoint. You don't replace a mind and personality like Barney's every day."
Paul's retirement is also significant. Well known for his controversial views on the Federal Reserve Board, which he famously proposed abolishing, Paul has served as chairman of the monetary policy subcommittee since January 2011.
Other notable retiring lawmakers included Miller, who was a leading House voice on housing issues and breaking up the big banks. Miller worked across chambers with Sen. Sherrod Brown to introduce bills to impose size and leverage limits on the largest banks and separate legislation designed to prevent foreclosures.
Several committee members also lost tough races. Rep. Judy Biggert, a Republican from Illinois, lost by a wide margin to former Democrat Rep. Bill Foster. Biggert, a seven-term lawmaker, serves as chairman of the subcommittee on insurance, housing and community opportunity, and has been a key voice on the panel for the insurance industry.
Foster sat on the banking panel during his earlier tenure in the House, and may likely return to the position, observers said.
"I absolutely believe he's going to be back on the panel, especially given that he's replacing Biggert," said Boltansky. "He was a full-throated advocate for Dodd-Frank, which is obviously a departure from Biggert's stance on the matter."
California Democrat Rep. Joe Baca also lost in an upset to challenger Gloria Negrete McLeod, a fellow Democrat.
Meanwhile, the GOP lost four freshman committee members who were all locked in tight races: Reps. Nan Hayworth of New York, Robert Dold of Illinois, Francisco "Quico" Canseco of Texas and Frank Guinta of New Hampshire. Earlier, Illinois Republican Rep. Donald Manzullo lost a close primary battle to freshman GOP Rep. Adam Kinzinger, who went on to win the general election.