Paul Bryant was the 11th of 12 children who were born to Wilson Monroe and Ida Kilgore Bryant in Moro Bottom, Cleveland County, Arkansas. His nickname stemmed from his having agreed to wrestle a captive bear during a carnival promotion when he was 13 years old. His mother wanted him to be a minister, but Bryant told her "Coaching is a lot like preaching". He attended Fordyce High School, where 6 ft 1 in (1.85 m) tall Bryant, who as an adult would eventually stand 6 ft 4 in (1.93 m), began playing on the school's football team as an eighth grader. During his senior season, the team, with Bryant playing offensive line and defensive end, won the 1930 Arkansas state football championship.

Bryant accepted a scholarship to play for the University of Alabama in 1931. Since he elected to leave high school before completing his diploma, Bryant had to enroll in a Tuscaloosa high school to finish his education during the fall semester while he practiced with the college team. Bryant played end for the Crimson Tide and was a participant on the school's 1934 national championship team. Bryant was the self-described "other end" during his playing years with the team, playing opposite the big star, Don Hutson, who later became a star in the National Football League and a Pro Football Hall of Famer. Bryant himself was second team All-Southeastern Conference in 1934, and was third team all conference in both 1933 and 1935. Bryant played with a partially broken leg in a 1935 game against Tennessee. Bryant pledged the Sigma Nu social fraternity, and as a senior, he married Mary Harmon, which he kept a secret since Alabama did not allow active players to be married.

After graduating from the University of Alabama in 1936, Bryant took a coaching job under A. B. Hollingsworth at Union University in Jackson, Tennessee, but he left that position when offered an assistant coaching position under Frank Thomas at the University of Alabama. Over the next four years, the team compiled a 29–5–3 record. In 1940, he left Alabama to become an assistant at Vanderbilt University under Henry Russell Sanders. During their 1940 season, Bryant served as head coach of the Commodores for their 7–7 tie against Kentucky as Coach Sanders was recovering from an appendectomy. After the 1941 season, Bryant was offered the head coaching job at the University of Arkansas. However, Pearl Harbor was bombed soon thereafter, and Bryant declined the position to join the United States Navy. In 1942 he served as an assistant coach with the Georgia Pre-Flight Skycrackers.

In 1945, 32-year-old Bryant met Washington Redskins owner George Marshall at a cocktail party hosted by the Chicago Tribune, and mentioned that he had turned down offers to be an assistant coach at Alabama and Georgia Tech because he was intent on becoming a head coach. Marshall put him in contact with Harry Clifton "Curley" Byrd, the President and former football coach of the University of Maryland.

Bryant coached at Kentucky for eight seasons. Under Bryant, Kentucky made its first bowl appearance in 1947 and won its first Southeastern Conference title in 1950. The 1950 Kentucky Wildcats football team finished with a school best 11-1 record and concluded the season with a victory over Bud Wilkinson's #1 ranked Oklahoma Sooners in the Sugar Bowl. The final AP poll was released before bowl games in that era, so Kentucky ended the regular season ranked #7. But several other contemporaneous polls, as well as the Sagarin Ratings System applied retrospectively, declared Bryant's 1950 Wildcats to be the national champions, but neither the NCAA nor College Football Data Warehouse recognizes this claim.. Bryant also led Kentucky to appearances in the Great Lakes Bowl, Orange Bowl, and Cotton Bowl Classic. Kentucky's final AP poll rankings under Bryant included #11 in 1949, #7 in 1950, #15 in 1951, #20 in 1952, and #16 in 1953. The 1950 season was Kentucky's highest rank until it finished #6 in the final 1977 AP Poll.

Though he led Kentucky's football program to its greatest achievement, Bryant resigned after the 1953 season because he felt that Adolph Rupp's basketball team would always be the school's primary sport. Years after leaving Lexington, Bryant had a better relationship with Rupp. For instance, Bryant was Alabama's athletic Director in 1969 and called Rupp to ask if he had any recommendations for Alabama's new basketball coach. Rupp recommended C. M. Newton, a former backup player at Kentucky in the late 1940s. Newton went on to lead the Crimson Tide to three straight SEC titles.

In 1954, Bryant accepted the head coaching job at Texas A&M University. He also served as athletic Director while at Texas A&M.

At the close of the 1957 season, having compiled an overall 25–14–2 record at Texas A&M, Bryant returned to Tuscaloosa to take the head coaching position, succeeding J.B. "Ears" Whitworth, as well as the athletic Director job at Alabama.

Bryant took over the Alabama football team in 1958. When asked why he came to Alabama, he replied "Momma called. And when Momma calls, you just have to come runnin'." Bryant's first spring practice back at Alabama was much like what happened at Junction. Some of Bryant's assistants thought it was even more difficult, as dozens of players quit the team. After winning a combined four games in the three years prior to Bryant's arrival, the Tide went 5–4–1 in Bryant's first season. The next year, in 1959, Alabama beat Auburn and appeared in the inaugural Liberty Bowl game, the first time either had happened in the last six years. In 1961, under his leadership, with quarterback Pat Trammell and football greats Lee Roy Jordan and Billy Neighbors, Alabama went 11–0 and defeated Arkansas 10-3 in the Sugar Bowl to claim the national championship.

In 1962, Bryant filed a libel suit against The Saturday Evening Post for printing an article by Furman Bisher ("College Football is Going Berserk") that charged him with encouraging his players to engage in brutality in a 1961 game against the Georgia Tech Yellow Jackets. Six months later, the magazine published "The Story of a College Football Fix" that charged Bryant and Georgia Bulldogs athletic Director and ex-coach Wally Butts with conspiring to fix their 1962 game together in Alabama's favor. Butts also sued Curtis Publishing Co. for libel. The case was decided in Butts' favor in the US District Court of Northern Georgia in August 1963, but Curtis Publishing appealed to the Supreme Court. As a result of Curtis Publishing Co. v. Butts 388 U.S. 130 (1967), Curtis Publishing was ordered to pay $360,000 in damages to Butts. The case is considered a landmark case because it expanded the definition of who can be considered a "public figure" in libel cases. Bryant reached a separate out-of-court settlement on both of his cases for $300,000 against Curtis Publishing in January 1964.

The 1967 team was billed as another national championship contender with star quarterback Kenny Stabler returning, but the team stumbled out of the gate and tied Florida State 37–37 at Legion Field. The season never took off from there, with the Bryant-led Alabama team finishing 8–2–1, losing 20-16 in the Cotton Bowl Classic to Texas A&M, coached by former Bryant player and assistant coach Gene Stallings. In 1968, Bryant again could not match his previous successes, as the team went 8–3, losing to the University of Missouri 35–10 in the Gator Bowl. The 1969 and 1970 teams finished 6–5 and 6–5–1 respectively.

Bryant was a heavy smoker and drinker, and his health began to decline in the late 1970s. He collapsed of a cardiac episode in 1977 and decided to enter alcohol rehab, but after a few months of sobriety, he resumed drinking. Bryant experienced a mild stroke in 1980 that weakened the left side of his body and another cardiac episode in 1981 and was taking a battery of medications in his final years.

In 1971, Bryant began engineering a comeback. This included abandoning Alabama's old power offense for the relatively new wishbone formation. (Darrell Royal, the Texas football coach whose assistant Emory Bellard virtually invented the wishbone, taught Bryant its basics, but Bryant developed successful variations of the wishbone that even Royal had never used.) The change helped make the remainder of the decade a successful one for the Crimson Tide. That season, Alabama went undefeated and earned a #2 ranking, but lost to #1 Nebraska, 38–6 in the Orange Bowl. The team would go on to split national championships in 1973 (Notre Dame defeated Alabama 24-23 in the Sugar Bowl, and the UPI thereafter stopped giving national championships until after all the games for the season had been played – including bowl games) and 1978 (despite losing a regular season matchup against national co-champion USC) and win it outright in 1979 after a 24-9 Sugar Bowl victory over Arkansas.

Ozzie Newsome is active as the general manager of the Baltimore Ravens. He was a Professional Football Hall of Fame tight end for the Cleveland Browns for 13 seasons (1978–90) and stayed loyal to owner Art Modell after the move to Baltimore. Newsome was the GM of the Ravens' Super Bowl XXXV championship team in 2000, and their Super Bowl XLVII championship team in 2012.

In a 1980 interview with Time magazine, Bryant admitted that he had been too hard on the Junction Boys and "If I were one of their players, I probably would have quit too."

Many of Bryant's former players and assistant coaches went on to become head coaches at the collegiate level and in the National Football League. Danny Ford (Clemson, 1981), Howard Schnellenberger (Miami of Florida, 1983), and Gene Stallings (Alabama, 1992) all won national championships as head coaches for NCAA programs while Joey Jones, Mike Riley, and David Cutcliffe are active head coaches in the NCAA. Charles McClendon, Jerry Claiborne, Sylvester Croom, Jim Owens, Jackie Sherrill, Bill Battle, and Pat Dye were also notable NCAA head coaches. Croom was the SEC's first African-American head coach at Mississippi State from 2004 through 2008. Arizona Cardinals head coach Bruce Arians was a running backs coach under Bryant in 1981–82.

After a sixth-place SEC finish in the 1982 season that included losses to LSU and Tennessee each for the first time since 1970, Bryant, who had turned 69 that September, decided to retire, stating, "This is my school, my alma mater. I love it and I love my players. But in my opinion, they deserved better coaching than they have been getting from me this year." His last regular season game was a 23–22 loss to Auburn and his last postseason game was a 21–15 victory in the Liberty Bowl in Memphis, Tennessee, over the University of Illinois. After the game, Bryant was asked what he planned to do now that he was retired. He replied "Probably croak in a week." His reply proved eerily prophetic.

Four weeks after making that comment, and just one day after passing a routine medical checkup, on January 25, 1983, Bryant checked into Druid City Hospital in Tuscaloosa after experiencing chest pain. A day later, when being prepared for an electrocardiogram, he died after suffering a massive heart attack. His personal physician, Dr. william Hill, said that he was amazed that Bryant had been able to coach Alabama to two national championships in the last five years of his life with the state of his health. First news of Bryant's death came from Bert Bank (WTBC Radio Tuscaloosa) and on the NBC Radio Network (anchored by Stan Martyn and reported by Stewart Stogel). On his hand at the time of his death was the only piece of jewelry he ever wore, a gold ring inscribed "Junction Boys". He is interred at Birmingham's Elmwood Cemetery. A month after his death, Bryant was posthumously awarded the Presidential Medal of Freedom, the nation's highest civilian award, by President Ronald Reagan. A moment of silence was held prior to Super Bowl XVII, played four days after Bryant's passing.

Bryant was portrayed by Gary Busey in the 1984 film The Bear, by Sonny Shroyer in the 1994 film Forrest Gump, Tom Berenger in the 2002 film The Junction Boys, and Jon Voight in the 2015 film Woodlawn.

The Aggies suffered through a grueling 1-9 initial season which began with the infamous training camp in Junction, Texas. The "survivors" were given the name "Junction Boys". Two years later, Bryant led the team to the Southwest Conference championship with a 34–21 victory over the University of Texas at Austin. The following year, 1957, Bryant's star back John David Crow won the Heisman Trophy (the only Bryant player to ever earn that award), and the Aggies were in title contention until they lost to the #20 Rice Owls in Houston, amid rumors that Alabama would be going after Bryant.