Valenzuela was born in Navojoa, Mexico sometime between 1955 and 1960. His birthdate is officially listed as November 1, 1960, but most baseball scouts and media believe he was born up to five years earlier. In any case, he entered organized baseball in 1978 with the Guanajuato team of the Mexican Central League. During the following season, in which Valenzuela pitched for Yucatan in the Mexican League, he drew serious attention from major league scouts and was acquired by the Dodgers on July 6, 1979.

Valenzuela spent a few weeks in the Dodgers' minor-league system that year and then rang up a solid season at Double-A San Antonio in 1980. He was called up in September and pitched brilliantly down the stretch run, tossing 17 2/3 innings of shutout baseball out of the bullpen with two wins and a save. His work helped the Dodgers tie the Houston Astros for the 1980 National League West Division title, although they lost it in a one-game playoff.

His efforts made him the odds-on favorite to be the league's top rookie in 1981, and he didn't disappoint, starting the season 8-0 with four shutouts and an ERA under 1.00. He became an instant media icon, a huge drawing card to the Los Angeles Hispanic community, and triggered a mad race to acquire his rookie baseball cards. After a strike wiped out a third of the season, he cooled down a bit, but still finished 13-7 with a 2.48 ERA and led the league with 180 strikeouts. He ended the season as the only pitcher to win Rookie of the Year and Cy Young Award honors in the same year. He pitched a complete game in Game 3 of the 1981 World Series against the New York Yankees

Valenzuela had three trademarks which followed him in his great seasons. One was his physique--like some other pitchers of his time such as David Wells and Rick Reuschel, he was slightly overweight. He was also known for a devastating screwball, which right-handed hitters flailed away at ineffectually. And last but not least, in an era of poor hitting pitchers, he had seasons where he hit better than some Dodgers regulars.

Following the outstanding debut, Valenzuela settled down into a number of years as a workhorse starter and one of the league's best pitchers. He had his best season in 1986, when he finished 21-11 with a 3.14 ERA and led the league in wins, complete games and innings pitched. He lost a narrow vote for the Cy Young Award to the Astros' Mike Scott.

At the 1986 All-Star Game, Valenzuela made history by striking out five consecutive American League batters, tying a record set by fellow screwballer Carl Hubbell in the 1934 contest.

In 1987, he began to slump, dropping off to 14-14 with a 3.98 ERA. By 1988, when he won just five games and missed much of the season (ironically, in a year in which the Dodgers won the World Series), it was obvious he had a dead arm.

No longer blessed with his great screwball, he came back in 1989 and went 10-13, improving to 13-13 a year later. He had one last great moment on June 29, 1990, when he threw a 6-0 no-hitter against the St. Louis Cardinals just hours after the Oakland Athletics' Dave Stewart had thrown one against the Toronto Blue Jays. In fact, Valenzuela watched Stewart's no-hit game on television and told his teammates he was going to throw one too.

After pitching ineffectively in spring training in 1991, he was released by the Dodgers. An abortive attempt at a comeback with the California Angels failed later that summer. He returned to the Mexican League, where he pitched and played some first base when he wasn't on the mound, before making another brief comeback in 1993 with the Baltimore Orioles.

Jumping between the big leagues and Mexico for the next few seasons, he put together one more solid big-league season in 1996 for the San Diego Padres, going 13-8 with a 3.62 ERA. He retired a year later with a final record of 173-153 and a 3.54 ERA.

During the early parts of his 10 years with the Dodgers, Valenzuela caused a large frenzy among his fans, and that affection that the fans felt for Valenzuela became popularly known as Fernandomania.

In 2003, he returned to the Dodger organization as the Spanish-language radio color commentator for National League West games, joining Jaime Jarrin and Pepe Yniguez in the Spanish-language booth.

On June 29, 2004, Valenzuela announced he would return to the mound in the Liga Mexicana del Pacífico (the Mexican Pacific Coast League) in October at which time he was nearly 44 years old. He pitched again that Mexican winter league, during the 2005-06 season.

After a period of eligibility of three years, in 2004 Valenzuela failed to garner the requisite 5f votes (he received 19 with the threshold for that year being 25) necessary to remain on the following year's ballot. Valenzuela's last opportunity for Hall of Fame consideration remains with the Veterans Committee, where his name will appear on their ballot no earlier than 2018, twenty years from the date of his retirement.

In 2005, he was named one of three starting pitchers on Major League Baseball's Latino Legends Team.

His son, Fernando Jr., current plays in the San Diego Padres organization as a first baseman.