Gomez grew up in California and played for the San Francisco Seals after high school. He made his MLB debut with the Yankees in April 1930. He was selected as an All-Star every year between 1933 and 1939. He sustained an arm injury in 1940. Though he rebounded well in 1941, he pitched his last full season in 1942, then appeared in one game in 1943 before retiring with the Washington Senators.
In 1933, Gomez married June O'Dea, who had a brief career as a Broadway actress. After his retirement, he became a popular public speaker. Gomez was elected to the National Baseball Hall of Fame by the Veterans Committee in 1972. He made an appearance at Yankee Stadium in 1987, when he and Whitey Ford were honored with plaques at the stadium's Memorial Park. He died in California in 1989.
Gomez was born in Rodeo, California. His father, Francisco Gomez, had been born in California to a Spanish father, Juan Gomez, and a Portuguese mother, Rita. His mother, Lizzie Herring, was an American of Welsh-Irish descent. He played sandlot baseball in Oakland while attending Richmond High School and was recruited by the San Francisco Seals. The New York Yankees purchased Lefty from the Seals for an estimated $39,000.
Gomez made his major league debut on April 29, 1930. He pitched in only 15 games and finished the season with a 2-5 win-loss record, a 5.55 earned run average (ERA). Coming into the 1931 season, Gomez had good pitching velocity, but the Yankees were concerned about the pitcher's slender frame of 6 feet 2 inches (1.88 m) and 155 pounds (70 kg). Following a common medical strategy of the time, the team had most of his teeth extracted; they also had him drink three quarts of milk daily and gave him an unlimited meal allowance for road games. Gomez registered the second-best ERA in the American League in 1931.
A 20-game winner four times and an All-Star every year from 1933 to 1939, Gomez led the league twice each in wins, winning percentage and ERA; he was a three-time league leader in shutouts and strikeouts. In the first major league All-Star Game (July 6, 1933), Gomez was the winning pitcher for the American League (AL) and drove in the first run of the game. This was out of character for him; he was notorious for poor hitting even by AL standards. Late in life, Lopez commented, "I never even broke a bat until last year when I was backing out of the garage." His career OPS+ of -7 is the fifth-worst in baseball history among players with at least 1,000 plate appearances. Gomez holds the record for the most innings pitched in a single All-Star game (six, in 1934).
Lefty's best season came in 1934, when he won 26 games and lost just five. In both 1934 and 1937, he won pitching's "Triple Crown" by leading the league in wins, ERA and strikeouts; he also led the AL both seasons in shutouts. His .649 career winning percentage ranks 15th in major league history among pitchers with 200 or more decisions. Among pitchers who made their MLB debuts from 1900 to 1950, only Lefty Grove, Christy Mathewson and Whitey Ford have both more victories and a higher winning percentage than Gomez.
Gomez won six World Series games without a loss, a career World Series record. He won a World Series game in 1932, two in 1936, two in 1937 and one in 1938. He also set a World Series record by receiving two walks in the same inning on October 6, 1937.
Nicknamed "El Goofo" and "Goofy Gomez", he was known for his sense of humor, even on the field. In one game, he came up to bat when it was slightly foggy. Bob Feller was on the mound and Gomez struck a match before stepping into the batter's box. "What's the big idea?" asked the umpire. "Do you think that match will help you see Feller's fast one?" Gomez replied, "No, I'm not concerned about that. I just want to make sure he can see me!" Another time, a reporter asked the noted brushback pitcher, "Is it true that you'd throw at your own mother?" Gomez replied, "You're damn right I would. She's a good hitter." Gomez also often remarked, "I'd rather be lucky than good."
In 1940, Lefty suffered an arm injury, which left him up for grabs by another team, but in 1941 he played fairly well, winning 15 and losing 5. During that season, he was said to be a great starting pitcher, but won through the support of Johnny Murphy, who relieved him in later innings. After the 1942 season ended, Lefty took a job as a dispatcher with the General Electric River Works, a defense plant in Lynn, Massachusetts, which only paid $40 a week. Then on January 27, 1943, the Yankees sold Lefty to the Boston Braves for $10,000.
Lefty never appeared in a game with the Braves, as later in the year he was released from his contract and signed with the Washington Senators. He pitched just one game before retiring from the game. In his career, almost entirely spent with the Yankees, he had a 189–102 record with 1,468 strikeouts and a 3.34 ERA in 2503 innings pitched.
On February 26, 1933, Lefty married June O’Dea (1912-1992). A Broadway headliner who starred in Of Thee I Sing, she gave up her career in 1936. By 1937 the marriage was on shaky ground. Lefty traveled to Hollywood that April and June returned to Massachusetts to stay with family. Through the tabloids, she learned in December that Lefty was filing divorce papers in Mexico, charging incompatibility. Being a devout Catholic, June refused a divorce but agreed to a formal separation, citing abandonment and cruel and inhuman treatment. Publicly, Lefty said the whole idea of divorce was absurd, but after the first of the year he moved to Reno to get a six-week divorce. It was his intention for the divorce to be finalized by the time he began spring training in Florida. Separation proceedings continued for months, but were called off in May 1938. Lefty and June went on to have two daughters and two sons.
In retirement, Gomez became a sought-after dinner speaker known for his humorous anecdotes about his playing days and the personalities he knew. He was a bit of a screwball, nicknamed "El Goofo" or "Goofy Gomez" (a likewise-alliterative counterpart to his contemporary, Dizzy Dean), and delighted in playing practical jokes on everyone from teammates to umpires. On February 2, 1972, the Veterans Committee unanimously inducted Gomez into the National Baseball Hall of Fame, along with Giants outfielder Ross Youngs and former American League President Will Harridge. The Committee noted that Lefty pitched in seven World Series games with no losses and five wins. Wearing a Yankee cap, Gomez became the second player of Hispanic descent to be inducted.