After an All-American career at the University of Tulsa, Largent was selected in the fourth round of the 1976 NFL draft by the Houston Oilers. After four preseason games, he was initially slated to be cut, but instead he was traded to the expansion Seattle Seahawks for a 1977 eighth-round pick. Largent spent 14 years with the Seahawks, and, while not particularly fast, was extremely sure-handed. He was selected to the NFL Pro Bowl seven times, and was the first Seahawk to earn the honor. His #80 jersey was retired in 1990, and as of 2005 he is the only Seahawk to be so honored (although the team has retired #12 in honor of the fans, the so-called "twelfth man").

He was inducted into the Pro Football Hall of Fame in 1995, the first Seahawks player to be so honored. Two other Hall of Famers played for the team: defensive end Carl Eller and running back Franco Harris, but both of these men played for the Seahawks only briefly at the end of their careers and were enshrined as members of the Minnesota Vikings and the Pittsburgh Steelers, respectively.

When Largent retired he held every major career record for receivers, all of which have since been broken by Jerry Rice. During Rice's stint with the Seahawks in 2004, Largent's #80 was temporarily "unretired" (with his approval) permitting Rice to continue to wear the number he had used for his entire career. Largent remains the most prolific receiver in team history.

Largent returned to Tulsa in 1989 and soon became active in politics. However, he didn't make his first run for office until 1994. That year, 1st District Congressman Jim Inhofe ran in a special election to succeed Senator David Boren, Largent entered the Republican primary for the Tulsa-based district. He won the nomination and went on to win easily in November. He was reelected three times, never winning less than 60 percent of the vote in the heavily Republican district.

Like many of his colleagues in the Republican freshmen elected in 1994 - when the Republicans took control of the House for the first time in 40 years - Largent's voting record was strongly conservative. However, Largent was one of the "true believers" in that freshman class. He devoted most of his time to issues important to the religious right. One of his first bills was a "parental rights" bill that died in committee after it attracted opposition even from other Christian conservatives. Another one of his early bills would have abolished the federal tax code at the end of 2001, a measure that only made Republicans appear fiscally irresponsible in the press. He opposed ending the 1996 federal government shutdown, and when it ended was one of the major players in an attempted coup against House Speaker Newt Gingrich. After the Republicans suffered heavy losses in the 1998 midterm elections, Largent was one of a group of Republican congressmen who drove Gingrich into retirement.

Largent himself tried to take advantage of discontent with Majority Leader Dick Armey by challenging Armey for the post. Armey was very unpopular in the Republican caucus, but managed to defeat Largent because Largent wasn't seen as a team player. However, the bruising contest all but ended Armey's chances of becoming Speaker.

Despite this, Largent decided to run for Governor of Oklahoma in 2002. He easily won the Republican nomination and resigned his House seat to devote all his energy to the race. Initially seen as an overwhelming favorite against Democratic state senator Brad Henry, his campaign lost ground since most Oklahomans outside of the Tulsa area didn't know where he stood on issues.

Perhaps his biggest misstep occurred when he swore at an Oklahoma City television reporter who wanted to know where he was at the time of the September 11, 2001 attacks. His Press Secretary had put out a statement as if it were from Largent and then it was learned that Largent was on a hunting trip and didn't find out about the events of 9/11 until day or so later. Largent lost to Henry by just under 7,000 votes.

Currently the CEO of the CTIA since 2003. CTIA is the lobbying organization for the cellular phone industry.