Shuler’s athletic career began at Swain County High School in Bryson City. A standout quarterback who led his team to two state championships, he was named as the North Carolina High School Player of the Year. He attracted scout attention and accepted an athletic scholarship to the University of Tennessee in 1990.

Under head coaches Johnny Majors and Phillip Fulmer, Shuler gained national attention as one of the SEC’s top quarterbacks. After a limited role in the 1991 season behind quarterback Andy Kelly, he became a prolific passer. In the 1992 season, he passed for 1,712 passing yards, ten touchdowns, and four interceptions as Tennessee finished with a 9–3 record. The next season, he finished with 2,354 passing yards, 25 touchdowns, and eight interceptions as Tennessee finished with a 9–2–1 record. He held nearly all Volunteer passing records by the end of his collegiate career; most were subsequently eclipsed by Peyton Manning. In 1993, Shuler came in second behind Charlie Ward in the vote for the Heisman Trophy.

Shuler was a first-round selection in the 1994 NFL Draft, taken by the Washington Redskins with the third overall pick. He held out of training camp until he received a 7-year, $19.25 million contract, most of the holdout being due to Shuler’s agent and the Redskins general manager discussing the parameters of the contract. The Redskins had fallen on hard times since winning Super Bowl XXVI, and Shuler was considered the quarterback of the future. However, Shuler’s poor play contributed to a quarterback controversy with fellow 1994 draft pick, seventh-rounder Gus Frerotte. Public and fan sentiment soon began to back Frerotte, especially after Shuler threw five interceptions in a 19–16 loss to the Arizona Cardinals. Shuler started 18 games in his first two years with the team and was benched in his third year, as Frerotte led the team.

After the 1996 season, Shuler was traded to the New Orleans Saints for a fifth-round pick in the 1997 draft and a third-round pick in 1998. Shuler’s statistics remained poor. He suffered a serious foot injury during the 1997 season in New Orleans and had two surgeries to try to correct it. Football statistics site Football Outsiders called Shuler “The least valuable quarterback of 1997.”

After retiring from the NFL, Shuler returned to the University of Tennessee and completed his degree in psychology. He became a real estate professional in Knoxville, Tennessee. His real estate company is one of the largest independent firms in East Tennessee. In 2003, Shuler moved to Biltmore Forest, North Carolina.

After being unable to take the field due to his foot injury in his second season in New Orleans, Shuler signed with the Oakland Raiders. After re-injuring his foot in training camp, he was cut and later retired. As a professional, his career passer rating was a 54.3. In 2004, ESPN rated him the 17th biggest ‘sports flop’ of the past 25 years, along with the fourth biggest NFL Draft bust. In 2007, the NFL Network ranked Shuler as the ninth-biggest bust in NFL history.

In July 2005, Shuler announced his intention to seek the Democratic nomination to run against eight-term incumbent Republican Charles H. Taylor. North Carolina’s 11th congressional district covered most of the Western North Carolina mountains where Shuler grew up.

In the November election, Shuler won with 54 percent of the vote to Taylor’s 46 percent. He carried nine of the district’s 15 counties, including several that had reliably supported Taylor over the years. He even won Taylor’s home county of Transylvania. Shuler was one of only two Democrats to defeat an incumbent in the South that year. His victory gave the Democrats a majority of the state’s congressional delegation for the first time since the 1994 elections. North Carolina’s 11th was one of thirty seats picked up by Democrats nationwide in 2006, giving them control of the House for the first time since 1994.

In 2007, Shuler introduced proposed legislation co-sponsored with fellow North Carolina U.S. Congressman Walter Jones to require airlines to have sections of the aircraft where large movie screens would not be visible.

In 2008, Shuler faced Carl Mumpower, a Republican Asheville city councilman, and Libertarian Keith Smith. Shuler won strongly with 62 percent of the vote. He easily carried all 15 counties in the district, including the traditionally Republican Henderson County.

In 2009, a documentary film about the successful 2006 Democratic campaign to retake control of the House, HouseQuake, prominently featured then-Congressman Rahm Emanuel’s efforts to recruit new candidates including Shuler. “Mr. Emanuel’s efforts to get him to run offer one of the most revealing moments in the film,” including two weeks of frequent phone calls about the balancing of family and Congressional obligations. The film was directed and produced by Karen Elizabeth Price, daughter of Congressman David Price who represents North Carolina’s 4th congressional district.

In early 2009, Shuler was mentioned as a possible candidate to run against incumbent Republican Richard Burr for the United States Senate in the next year’s elections. He ultimately chose not to do so, and sought reelection to the House. Shuler defeated Republican nominee Jeff Miller, winning reelection by a margin of 54% to 46%.

In April 2009, Shuler voted against the Matthew Shepard and James Byrd Jr. Hate Crimes Prevention Act.

In Washington, Shuler lived at the C Street House of The Fellowship, a controversial organization which operates the property as a tax-exempt church and a residence for several congressmen and senators. The building became notorious during a series of political sex scandals in 2009, in which current or former residents John Ensign, Mark Sanford, and Chip Pickering admitted to adulterous affairs, which their housemates knew of but did not publicize. In September 2010, The New Yorker published a piece about the house, focusing on the connection with a secretive religious organization called the Fellowship. Shuler has attended weekly prayer sessions sponsored by the group since his arrival in Washington. In reference to the secrecy, Shuler said “I’ve been here the whole time, and there’s talk about what the Fellowship is, but I honestly have no idea what they’re talking about. I honestly don’t know what it is.”

During his 2010 campaign, Shuler showed interest in taking the place of Nancy Pelosi as Speaker of the House, if Democrats maintained their majority. On November 4, after Republicans had won a majority of seats in the upcoming Congress, Shuler predicted Pelosi would no longer be a leader in the House. However, if Pelosi wanted to take the minority leader position, Shuler told Roll Call, he would run against her if there were no “viable candidate”.

On November 13, 2010, in a long New York Times article about Shuler, Campbell Robertson noted his use of a football analogy to describe the current situation of Congressional Democrats: “It’s no different than me as a quarterback,” he said. “I didn’t play very good. So what they’d do? They benched me.” Robertson noted that “Shuler has emerged as one of most prominent voices in the debate on the Democratic Party’s immediate future. He was among the first to call for Ms. Pelosi to step down from her leadership role in the new Congress and said he would run for minority leader himself if no alternative emerged (though he admitted that he would be an underdog).” According to Robertson, Shuler felt the Democratic leadership “has been too reflexively partisan” and called for “a more moderate approach.”

In July 2011, the Republican-dominated General Assembly significantly redrew the 11th. The district and its predecessors had been anchored in Asheville for over a century. However, the new map saw most of heavily Democratic Asheville drawn into the 10th. To make up for the population loss, a number of heavily Republican counties in the Foothills were moved to the 11th. The redistricting reduced the percentage of registered Democrats in the 11th from 43% to 36%. Chris Cooper, a political science professor at Western Carolina University, concluded that the new district was so heavily Republican that Shuler would need to “practically completely separate himself from the Democratic party” in order to have any chance of winning a fourth term. Years later, NBC News also concluded that the redrawn 11th was all but unwinnable for a Democrat, even one as conservative as Shuler. The district was drawn in a way that in some neighborhoods, one side of the street moved to the 10th while the other side remained in the 11th.

In 2011, Shuler led a group of House Democrats in pressuring the President to deal with the AT&T and T-Mobile merger. The group pushed for the lawsuit to be settled by the Department of Justice. The group sided with the claim made by AT&T that the merger would create much-needed jobs.

In November 2011, Shuler took the lead in a bipartisan call calling for larger cuts of the U.S. deficit.

Shuler voted against the Emergency Economic Stabilization Act of 2008 both times it came before the House. He later joined seven other conservative House Democrats in voting against the American Recovery and Reinvestment Act of 2009, an $819 billion economic stimulus bill proposed by President Barack Obama. Shuler also voted against the Affordable Health Care for America Act, or HR 3962, along with 38 other Democrats, despite voting yes on the Stupak amendment in the same bill, which prohibits federal funds to be used for abortions. In January 2011, Shuler voted against repealing the law, explaining that the repeal would be immoral.

In 2011, he co-sponsored HR 3, the No Taxpayer Funding for Abortion Act, The bill contained an exception for “forcible rape,” which opponents criticized as potentially excluding drug-facilitated rape, date rape, and other forms of rape. The bill also allowed an exception for minors who are victims of incest.

Shuler is a strong advocate of gun rights. On January 10, 2011, the Washington Post reported that “[i]n the wake of the shooting of Rep. Gabrielle Giffords,” Shuler “intends to arm himself more frequently” and is “encouraging his staff members to apply for carry permits.” On January 29, 2011, a Doonesbury cartoon made fun of Shuler’s plan to carry a gun.

In July 2011, Shuler was one of five Democrats to vote for the Cut, Cap, and Balance Act.

On February 2, 2012, Shuler announced that he would not run for another term. He endorsed his former chief of staff, Hayden Rogers, in the race to succeed him, but Rogers, as expected in the now heavily Republican district, lost the general election to Republican Mark Meadows. Years later, he told NBC News that the kind of ultra-precise redistricting that enabled the Republican-dominated legislature to split Asheville between two districts was bad for the country because it made it all but impossible to elect moderates to Congress. He argued that a fairer redistricting system was “the single greatest thing that could happen.”

Shuler transitioned to a lobbying position with Duke Energy to direct its lobbying and government affairs in Washington, D.C., in 2013.

In March 2020, He endorsed Joe Biden’s presidential bid.