Dean was a standout at Louisiana Tech University in Ruston, having spurned an opportunity to play for legendary coach Eddie Robinson at nearby Grambling State University, which at the time was sending African American players to the NFL on a yearly basis. Dean excelled as an All-Southland Conference defensive tackle during his collegiate football career at Louisiana Tech.
Dean was drafted by the Chargers in the 2nd round (33rd overall pick) 1975 NFL Draft. Dean recorded 15½ sacks in 1978. In 1979, the Chargers won the AFC West division while leading the AFC in fewest points allowed (246) and Dean was named to the All-AFC team. The Chargers again won the AFC West in 1980, with Dean teaming with fellow 1975 Charger draftees Gary "Big Hands" Johnson and Louie Kelcher as the Chargers led the NFL in sacks (60). Dean had missed the first two games of the season after not reporting, but still finished the season with 10 1⁄2 sacks. He and Johnson were named First-team All-Pro, with Kelcher being named Second-team All-Pro. The trio, along with Leroy Jones formed a defensive front that was locally nicknamed the Bruise Brothers.
In 1981, Dean, was traded to the San Francisco 49ers due to a contract dispute with Chargers' ownership. Dean contends he was making the same amount of money as his brother-in-law who was a truck driver. The Chargers' defense would not be the same afterwards, and Don "Air" Coryell's Chargers teams are now most remembered for its high-scoring, pass-oriented offense that did not have enough defense to make it to a Super Bowl. In 2013, U-T San Diego called the Chargers trading Dean "perhaps the biggest blunder in franchise history."
Dean was acquired mid-season by the 49ers and eventually helped them win two Super Bowls in the 1980s. His first game as a 49er was a key match-up against the Dallas Cowboys. Dean played after only a couple of practices and was still able to apply pressure and repeatedly hurried Danny White when he was not recording one of his 6 sacks, in a game won by the 49ers, 45-14. His first action of the season as a 49er was noted by author Tom Danyluk as "the greatest set of downs I have ever seen unleashed by a pass rusher". In what had been a game of possum, Bill Walsh, the 49er head coach, said to John Madden, who covered the game, "Fred (Dean) just got here . . . If he plays, he won't play much". But, he played the whole game.
His next home game for the 49ers was against the Los Angeles Rams. The game was won by the 49ers and the first win against the Rams in Candlestick Park, 20-17, as Dean sacked Pat Haden 5 times. He ended the season with 13 sacks, 12 with the 49ers and 1 with the Chargers, prior to his trade.
The 49ers went on to win the Super Bowl that year, and Steve Sabol (NFL Films) is quoted in 2006 as saying that Dean's acquisition was the last meaningful in-season trade, in that it affected the destination of the Lombardi Trophy. Dean that year won UPI NFC Defensive Player of the Year while playing in 11 games for the 49ers. San Diego's defense collapsed when Dean departed, giving up 40 points in a loss to the Cincinnati Bengals in the regular season, and 65 total points in playoff games vs. the Miami Dolphins and Bengals.
"I can't say how much it affected us, because we did make it to the AFC championship game," said Johnson of the Chargers without Dean. "But I could say if we had more pass rush from the corner, it might've been different.
The Charger defense did not return to the top half of the NFL rankings again until the unit was rebuilt in the late 1980s, and the club did not have an effective pass rusher until Leslie O'Neal was drafted in 1986.
In 1983 Dean recorded 17 sacks to lead the NFC and recorded a then-NFL record of 6 in one game, setting that mark during the 49ers’ 27-0 shutout of the New Orleans Saints on November 13, 1983. The 17 sacks was a Dean career high, bettering his 1978 total of 15½ with the Chargers. He followed that 1978 season by adding nine sacks in 1979 and 10½ in 1980. He had recorded 6½ sacks as a rookie in 1975. Dean's career sack total, with his unofficial numbers included, is 93.
Dean was also a key player on the 49ers 1984 Super Bowl team, mostly used as a situational pass rusher. During the 1984 season, Dean was reunited with his Charger teammates, Johnson, Kelcher and Billy Shields.
Dean was inducted into the Louisiana Tech University Athletic Hall of Fame in 1990. Dean is a member of the Louisiana Sports Hall of Fame. On August 2, 2008, Dean was elected to the Pro Football Hall of Fame. He was inducted at the enshrinement ceremony where his bust, sculpted by Scott Myers, was unveiled. In 2009 Dean was elected to the College Football Hall of Fame.