The 65-year-old Norwood, who also was a dentist, died at his home in Augusta, Ga., his office said.
The House observed a moment of silence for Rep. Norwood at 2 p.m., reports CBS News producer Allison Davis.
Norwood suffered from a chronic lung disease and later developed metastatic cancer that spread from his lung to his liver. He had declined further treatment last week and returned home to Georgia to receive hospice care.
"Charlie was a great member of this body and a friend to all," Rep. Nathan Deal, a fellow Georgia Republican, said on the House floor.
The vacancy created by Norwood's death won't be filled immediately. In Georgia, the governor submits an official request for a special election to the secretary of state. The request must be made within 10 days of the seat being vacated, with the election to be held no fewer than 30 days later.
A feisty, tobacco-chewing conservative who loved to hunt and who railed against government bureaucracy, Norwood came out of nowhere to beat Democratic incumbent Don Johnson in 1994. He became the first Republican to represent that northeastern Georgia district since shortly after the Civil War.
Friends say Norwood had hoped to follow that by becoming Georgia's first Republican governor in the modern era. He also considered a Senate bid, but deferred running for statewide office after he was diagnosed with the life-threatening lung disease in 1998.
Norwood had a dry wit and rarely settled for diplomatic language. When a Democrat complained that Norwood cut off questioning at a mine safety hearing last year, Norwood responded: "When you get in charge, you get to run the damn thing. Right now, you're not."
He wasn't shy to criticize his own party either when he thought it was veering off course, calling Republicans who backed compromise immigration legislation last year "turncoats."
Norwood prided himself on serving his northeast Georgia district, touting his success in cutting through federal regulations a decade ago to allow a constituent to bring home a stuffed polar bear the man had killed on a hunting trip in Canada.
It was that zeal for protesting governmental intrusions, along with his Southern charm, that earned Norwood easy re-election for most of his career, said David Barbee, a longtime friend and Republican Party leader in Augusta.
"I've seen him go to fish fries and what-not and there would be 500 people and he'd shake every hand there," Barbee said. "He was just a good people person."
Norwood's passion was health care. Taking on the insurance companies, he spent much of his political career pressing for a "patients' bill of rights" aimed at giving consumers better access to care, including greater ability to sue insurers.
More recently, Norwood pounced on the issue of immigration, saying the country faces a "true invasion" and calling for nearly 40,000 troops on the border. He also was one of just 33 House members to vote against renewing the Voting Rights Act last year, arguing that it discriminates against Southern states over long-past racial transgressions.
Born in Valdosta, Ga. on July 27, 1941, Norwood attended public schools before going off to boarding school at Baylor School, a military academy in Chattanooga, Tenn.
It was there that Norwood shot and killed a close friend as the two were playing quick-draw with what they thought was an unloaded pistol. A staunch advocate for gun rights, he said the accident convinced him that education and training are the best gun control, not restrictions.
He married his wife, Gloria, in 1962 while getting a bachelor's degree from Georgia Southern College. He then earned a doctorate in dental surgery from Georgetown University in Washington, where he was president of the dental school student body.
He volunteered for the U.S. Army and served a combat tour in the Vietnam War in 1968, earning two Bronze Stars.
Thirty years later, Norwood was diagnosed with idiopathic pulmonary fibrosis, which began restricting his ability to breathe and ultimately required a lung transplant in 2004.
After the surgery, he used oxygen and zipped around the Capitol in a motorized cart, earning a reputation for having a lead foot.
Cancer is a common side effect of the immune suppression drugs he took as a result of the transplant, and doctors last year discovered a small tumor on his non-transplanted lung. They removed the cancer with surgery, and Norwood's health improved. But shortly after the November election, doctors discovered the cancer had spread to his liver.
Norwood announced last week that he would forgo further treatment, returning home to Augusta for hospice care.
Norwood is survived by his wife, Gloria; two sons, Charles and Carlton; and four grandchildren.