Jurgensen took over as starting quarterback in 1955. He also retained a starting position in the defensive secondary. Duke ended the season with a 7-2-1 record along with an ACC co-championship, but did not go to a bowl because Maryland received the league's automatic bid to the Orange Bowl. That season Jurgensen completed 37 of 69 passes for 536 yards, three touchdowns and seven interceptions. He also rushed 54 times for 48 yards, and scored two touchdowns. He also punted four times for a 33.7 average and intercepted four passes for 17 yards.
Jurgensen's senior season in 1956 did not start well, when Duke lost to South Carolina, 7-0, in the season opener. This game marked Duke's first ACC loss, coming in the fourth year of the conference's existence. Duke finished the season with a 5-4-1 mark and Jurgensen ended up 28-59 for 371 yards. He threw six interceptions and two touchdown passes and rushed 25 times for 51 yards with three touchdowns. Jurgensen's final career stats included 77-156 passes for 1,119 yards, 16 career interceptions and six touchdowns. He also rushed for 109 yards and intercepted ten passes.
Jurgensen also played baseball briefly at Duke, but turned down an invitation to try out for the basketball team.
One of Jurgensen's most memorable games was on Thanksgiving Day 1965, when the Cowboys took a 21–0 lead at RFK Stadium. Jurgensen then threw for 411 yards, leading the team back to win 34–31. He rushed for a touchdown on an quarterback sneak and threw a game-winning 35-yard pass to Bobby Mitchell.
In 1967, Jurgensen broke his own record by passing for 3,747 yards and also set NFL single-season records for attempts (508) and completions (288). Unfortunately, he missed much of the 1968 season because of broken ribs and elbow surgery. In 1969, Vince Lombardi took over as the Redskins' head coach. That season, Jurgensen led the NFL in attempts (442), completions (274), completion percentage (62%) and passing yards (3,102). The Redskins went 7-5-2 and had their best season since 1955 (which kept Lombardi's record of never having coached a losing NFL team intact). Sadly, Lombardi died of cancer shortly before the start of the 1970 season. Jurgensen would later say that, of the nine head coaches he played for during his NFL career, Lombardi was his favorite.
The Redskins enjoyed a resurgence in the early 1970s under coach George Allen and made it as far as Super Bowl VII, losing to the Miami Dolphins. However, Billy Kilmer started in place of Jurgensen, who was again bothered by injuries in 1971 and 1972. During this time period, a quarterback controversy developed between the two, complete with fans sporting "I Love Billy" or "I Love Sonny" bumper stickers on their vehicles. The defensive-minded Allen preferred Kilmer's conservative, ball-control style of play to Jurgensen's more high-risk approach. Despite the controversy, Jurgensen was helpful to his rival. Even to this day, Kilmer still stays at Jurgensen's house when he is in town.
In 1974, at the age of 40 and in his final season, Jurgensen won his third NFL passing crown even though he was still splitting time with Kilmer. In what would be the final game of his NFL career, Jurgensen made his first and only appearance in an NFL postseason game in the Redskins' 19-10 loss to the Los Angeles Rams in the first round of the 1974 NFC playoffs. He came off the bench in relief of Kilmer and completed 6 of 12 passes but also threw three interceptions.
In many circles, Jurgensen is recognized as the finest pure passer of his time. A five-time Pro Bowl selection, he earned three NFL individual passing titles. He exceeded 400 yards passing in a single game five times, and threw five touchdown passes in a game twice. With a career rating of 82.6, his stats include 2,433 completions for 32,224 yards and 255 touchdowns. He also rushed for 493 yards and 15 touchdowns.