Phil Niekro, one of baseball’s greatest knuckleball pitchers, who rode a baffling, fluttering pitch to the Hall of Fame in a long career that lasted until he was 48, died Dec. 26 at age 81.

The Atlanta Braves announced his death of cancer but did not say where he died. Mr. Niekro lived in Flowery Branch, Ga.

While growing up in Ohio, Mr. Niekro learned the deceptive knuckleball from his father, but it took years before he reached the major leagues. He did not win his first big league game until he was 26, and it took two more years before he would become established in the starting rotation of the Atlanta Braves.

He played on mediocre teams for much of his career, and his unorthodox pitch — few pitchers employ the slow, unpredictable knuckleball because it is so hard to master — made Mr. Niekro an oddity during an era of hard-throwing pitching stars.

Yet Mr. Niekro, whose nickname was “Knucksie,” persevered as one of the game’s most durable and reliable pitchers, producing results that often equaled those of his more celebrated contemporaries, including Bob Gibson, Nolan Ryan, Steve Carlton, Ferguson Jenkins, Jim Palmer and Tom Seaver.

Mr. Niekro pitched 5,404 innings in the major leagues — more than any pitcher whose career began after 1910. In a three-year span from 1977 through 1979, he threw more than 1,000 innings; in today’s game, it is unusual for a starting pitcher to throw more than 200 innings in a season.

Mr. Niekro’s remarkable longevity was attributable to the knuckleball, which is thrown with less effort than conventional pitches such as the fastball, curveball and slider. In throwing the pitch, Mr. Niekro placed the fingernails of his index and middle fingers on top of the baseball, along a curving seam. When he released the pitch, he kept his wrist rigid and pushed the ball toward home plate. After that, the path of the pitch was largely a matter of chance.

“Nobody has ever given me a good, definite explanation as to why the ball does what it does,” Mr. Niekro told Sports Illustrated. “I’ve had people film it at 28,000 frames a second. I’ve had a guy do his college thesis on my knuckleball, but nobody’s made me understand it.

“The thing that I feel sort of guilty about is that with every other pitch, you try to make the ball do something, spin it to make it curve or sink or sail. All I try to do is make the ball do nothing.”

Thrown properly, a knuckleball has no rotation. It drifts toward the plate 20 to 30 mph slower than other pitches, dropping down while veering inside or outside, according to air currents, aerodynamics, the pitcher’s grip and the knuckleball’s diabolical whim. Catchers use an oversized mitt to block the pitch as it reaches home plate.

“To throw a pitch like that you have to be a craftsman,” longtime pitching coach Johnny Sain told Sports Illustrated in 1977. “That’s why so few people have been able to learn it.”

The knuckleball is hard to control and infuriatingly difficult to hit. After batting against Mr. Niekro, onetime New York Yankee Bobby Murcer said, “Trying to hit him is like trying to eat Jell-O with chopsticks.”

Early in his career, Mr. Niekro relied on an assortment of pitches and never threw his knuckleball with an opposing runner on third base, fearing that a wild pitch would allow the runner to score. In 1967, Braves backup catcher Bob Uecker — who later became a renowned baseball announcer and wit — suggested that Mr. Niekro use the knuckleball all the time.

With his newfound confidence, Mr. Niekro led the National League that year with a 1.87 earned run average, ahead of such future Hall of Famers as Gibson, Seaver, Gaylord Perry, Jim Bunning and Juan Marichal. Two years later, he had one of his best seasons, with a 23-13 record and a 2.56 ERA, as he led the Braves to the playoffs, only to lose to the New York Mets.

Mr. Niekro quietly became one of baseball’s most effective pitchers in the 1970s. At different times, he led the league in every major pitching category, including strikeouts (262 in 1977); victories (20 in 1974, and 21 in 1979 — tying his knuckleballing brother, Joe Niekro of the Houston Astros, that year); and winning percentage (.810, with a 17-4 record in 1982). He won five Gold Glove awards for his fielding and was named to five all-star teams.

In 1973, Mr. Niekro threw a no-hitter against the San Diego Padres. Three years later, against the Cincinnati Reds — who went on to win the World Series — he pitched a one-hit shutout, allowing the only hit in the ninth inning.

Mr. Niekro led the National League in complete games four times, with a career high of 23 in 1979. His 21-20 record that year made him the last pitcher to win and lose 20 games in the same season.

Late in 1982, at age 43, Mr. Niekro helped secure a playoff spot for the Braves by hitting a two-run homer and shutting out the Padres, 4-0.

The next year, Mr. Niekro had a middling 11-10 record and was often at odds with his manager, former teammate Joe Torre. At the end of the season, Mr. Niekro was released, angering fans in Atlanta, where he was one of the city’s most popular athletes.

He then signed with the Yankees and, for the next two years, pitched better than any pitcher on Atlanta’s staff, winning 16 games each in 1984 and 1985. On the final day of the 1985 season against the Toronto Blue Jays, the 46-year-old Mr. Niekro used an assortment of fastballs, curveballs, screwballs and looping “eephus” pitches to keep hitters off balance. He broke out his knuckleball to strike out the final batter, Jeff Burroughs, to win the game, 8-0.

It was the 300th win of his career, the traditional Hall of Fame benchmark for a pitcher.

“I decided if I was going to win the 300th,” Mr. Niekro said after the game, “I should finish it with a knuckleball. I figured there was no other way to finish the game than using the pitch that got me there.”

Philip Henry Niekro Jr. was born April 1, 1939, in Blaine, Ohio. The family later moved to Lansing, Ohio, near the West Virginia border. His mother was a homemaker, and his father was a coal miner and semipro pitcher.

The elder Niekro learned the knuckleball from a teammate and later taught the pitch to his two sons.

In high school, Mr. Niekro was an excellent all-around athlete. His neighbor and closest friend was John Havlicek, who became a Hall of Fame basketball player with the Boston Celtics.

Mr. Niekro signed with the Braves, then based in Milwaukee, for a $500 bonus and worked his way through the minor leagues before making his major league debut in 1964.

Released by the Yankees in 1986, Mr. Niekro caught on with the Cleveland Indians and won 18 more games. He had a brief stint with the Blue Jays before taking the mound one final time for the Braves late in the 1987 season, when he was 48. His No. 35 uniform had already been retired by the Braves.

Mr. Niekro later managed in Atlanta’s minor league system and was a fixture at spring training camps.

Survivors include his wife of 54 years, the former Nancy Ferrand; three sons; and two grandchildren.

Mr. Niekro finished his 24-year career with a 3.35 ERA and 318 wins — more than Seaver, Gibson, Palmer or Jenkins. His 121 victories after age 40 are a major league record. His brother, Joe, who died at 61 in 2006, won 221 games. Their combined 539 wins are the most by a pair of brothers in baseball history.

In 1997, Mr. Niekro was elected to the National Baseball Hall of Fame in Cooperstown, N.Y. His guests at the induction ceremony included the Colorado Silver Bullets, a women’s professional baseball team he managed for several years.

Mr. Niekro was the seventh Hall of Fame player to die in 2020; the others are Seaver, Gibson, Lou Brock, Whitey Ford, Al Kaline and Joe Morgan. Other than his onetime teammate Hoyt Wilhelm, he is the only pitcher in the Hall of Fame whose primary pitch was the knuckleball.

“Since I got elected, I keep asking myself, ‘What does this all mean?’ ” he told the Hartford Courant in 1997. “And all I keep seeing is me and my dad throwing knuckleballs back and forth.”