Green Bay had posted an undefeated 12–0–1 record and won the NFL title in 1929, the year before Herber was on the roster. In his first year, 1930, the Packers continued their success and won another title with Herber playing tailback in the famous Notre Dame Box formation. In 1931, with Herber throwing more than usual for that era to early greats like John "Blood" McNally, the Packers reeled off nine straight wins to start the season and held on to win a third straight title. No other team in NFL history, besides the Packers themselves in the 1960s, has won three consecutive titles.
The NFL didn't start keeping statistics until 1932—when they did that year, Herber finished as the top passer in the league with 639 yards and nine touchdowns. He won the passing title again in 1934 with 799 yards and eight touchdowns. But Herber reached his peak as a pro starting in 1935 with the arrival of Don Hutson, the league's first true wide receiver, who changed the game with his graceful moves, precise patterns, and superb hands. Herber loved to throw the ball long and was a perfect fit for Hutson's talent. Hutson's first NFL reception was an 83-yard touchdown pass from Herber on the first play of the game when the Packers beat the Chicago Bears, 7–0. In 1936, Herber and Hutson rewrote (temporarily) the NFL passing-receiving record book. Herber tossed a record 177 passes for a record 1,239 yards, and 11 touchdowns. Hutson set new records with 34 catches, 526 yards receiving, and eight touchdowns, all marks he would soon improve. Green Bay finished 10-1-1 and went to the NFL title game, which they won 21-6 over the Boston Redskins at the Polo Grounds in New York. In that game, Green Bay passed for 153 yards and Herber threw two touchdowns, one to Hutson.
Sharing time with another great passer, Cecil Isbell, Herber led the Packers to the title game again in 1938 and 1939. In the 1938 championship game, Green Bay lost to the New York Giants 23–17 at the Polo Grounds despite another touchdown pass from Herber. In 1939, Green Bay avenged that loss with a 27–0 drubbing of the Giants in Milwaukee. Herber threw for another touchdown in the 1939 title game. In 1940, Isbell began to get more playing time and Herber was waived at the end of training camp in 1941, and retired after 11 seasons with Green Bay.
At age 34, Herber came back to the draft-depleted NFL in 1944, answering a call to play for the New York Giants. Herber threw sparingly but efficiently, for 651 yards and six touchdowns. As usual for Herber-led teams, the Giants won their conference and went to the NFL title game. Herber's old squad, the Packers, still featuring Don Hutson, beat the Giants 14-7. Herber played one more forgettable season with the Giants in 1945 and then retired for good.
Overall, Herber passed for 8,041 yards, 81 touchdowns, and 106 interceptions. He led his teams to four NFL championships. At the time Herber retired for the first time in 1940, he had equaled Benny Friedman for the all-time lead in touchdown passes with 66. He added to his total later when he came out of retirement for a two year stint with the New York Giants.
Herber was the first great long thrower in the NFL and his success paved the way for truly "modern" quarterbacks Sammy Baugh and Sid Luckman. Herber was said to throw the ball with all five fingers on the laces, a peculiarity shared by no one else. It was his performance with Don Hutson, however, that made him a legend and assured his place in the Pro Football Hall of Fame in 1966. He was elected to the Wisconsin Athletic Hall of Fame in 1968.
During the NFL's 50th season celebration in 1969, Herber was selected to the All-1930s team in August. Two months later, he died of cancer at age 59 in Green Bay, and is buried at its Fort Howard Memorial Park.