Grove was a sandlot star in the Baltimore area during the 1910s. Grove didn’t play organized baseball until he was 19 years old. In 1920, he made his professional debut with the Martinsburg Mountaineers of the class-D Blue Ridge League, where he appeared in six games. In 59 innings pitched, Grove gave up just 30 hits, and he had an earned run average (ERA) of 1.68. His performance attracted the attention of Jack Dunn, Sr. (1872–1928), the manager/owner of the minor league Baltimore Orioles, who also discovered Babe Ruth.

Grove joined the Baltimore Orioles in 1920, while they were playing a half-century in the minor leagues of first the old Eastern League (1903–1914) and then after 1916, in the reorganized International League of AAA ball. Grove broke into the team’s pitching rotation at midseason and had a 12-2 record the rest of the way. The Orioles were in the middle of winning six straight IL titles from 1919 to 1925. Over the next four seasons, Grove posted marks of 25-10, 18-8, 27-10 and 26-6, leading the International League in strikeouts each season.

Grove married his childhood sweetheart, Ethel Gardner, in 1921. They had two children, Robert and Doris. The couple would later divorce after Grove had an affair with another woman.

Grove remained in the minor leagues through 1924, as owner Jack Dunn refused several offers from the majors to acquire him. At the time, the Orioles were an independent operation with no major league affiliation and the International League had declared its players not subject to a major league draft. Since the reserve clause in all contracts was honored throughout organized baseball, this meant that Grove had no way to reach the majors until the Orioles became willing to trade or sell his contract. Finally, early in 1925, Dunn agreed to sell Grove’s rights to Connie Mack (1862–1956) and his Philadelphia Athletics in the American League for $100,600 (equivalent to $1.47 million in 2019), the highest amount ever paid for a player at the time.

Grove battled injuries as a major league rookie and posted a 10-13 mark (which would prove his only losing record in 17 major league seasons), despite leading the league in strikeouts. Grove then settled down in 1926 and won the first of a record nine earned run average (ERA) titles with a mark of 2.51. In 1927, Grove won 20 games for the first time, and a year later he led the league in wins with 24.

The Athletics won the AL pennant in three successive seasons from 1929 to 1931, as well as consecutive World Series championships in 1929 and 1930. During the Athletics’ championship run, Grove led the way as the league’s top pitcher, posting records of 20-6, 28-5 and 31-4. In 1931, Grove led the league in wins, ERA (2.06), strikeouts (175), winning percentage, complete games, and shutouts. His 2.06 ERA was 2.32 runs below the league average. He was also chosen as league MVP in 1931, making him one of only a handful of pitchers to achieve this honor. His MVP award is the only one not enshrined in the National Baseball Hall of Fame in Cooperstown, New York, instead being housed at the George’s Creek Library in Lonaconing, Maryland.

As a hitter, Grove posted a .148 batting average (202-for-1,369) with 119 runs, 15 home runs, 121 RBI and 105 bases on balls. From 1929 through 1932, Grove had 56 RBI. Defensively, he recorded a .954 fielding percentage.

The Athletics contended for the next two seasons, but finished second to the New York Yankees in 1932 and third behind the Washington Senators and Yankees in 1933. In 1933, Grove became the first player in Major League Baseball history to strike out five times in a nine-inning game. On December 12, 1933, team owner Connie Mack traded Grove, along with Max Bishop and Rube Walberg, to the Boston Red Sox for Bob Kline, Rabbit Warstler and $125,000.

Grove was unable to contribute substantially during his first year in Boston, an arm injury holding him to an 8-8 record. In 1935, however, Grove returned to form with a 20-12 record and a league-leading 2.70 ERA. In the 1936 season, he had a 2.81 ERA (winning his 7th ERA title) while recording a 17-12 record and 130 strikeouts. Grove won his eighth ERA title a year later while having a 17-9 record along with 153 strikeouts. He pitched 262 innings for the season; this was his 11th and final season where he pitched over 200 innings. Grove continued to post outstanding records, including 14-4 in 1938 and 15-4 in 1939, as well as lead the AL in ERA four times between 1935 and 1939. He had a 7-6 record in 1940 while recording a 3.99 ERA with 62 strikeouts in 153.1 innings. In his last season, he won and lost 7 games, winning his 300th game on July 25 (giving up 6 runs on 12 hits, but winning 10-6), before losing his last three major league games, ending his career on September 28, pitching just one inning in the 2nd game of a doubleheader.

Grove retired in 1941 with a career record of 300-141. His .680 lifetime winning percentage is eighth all-time; however, none of the seven men ahead of him won more than 236 games. His lifetime ERA of 3.06, when normalized to overall league ERA and adjusted for the parks in which Grove played during his career, is fifth all-time among pitchers with at least 1,000 innings pitched (behind Mariano Rivera, Clayton Kershaw, Jim Devlin, and Pedro Martínez) at 48 percent better than average.

Grove was elected to the National Baseball Hall of Fame in 1947. He died in Norwalk, Ohio, on May 22, 1975 and was interred in the Frostburg Memorial Cemetery in Frostburg, Maryland.

In 1969, Grove was voted the left handed starting pitcher for Major League Baseball’s 100th anniversary team. In 1999, Grove was ranked number 23 on The Sporting News list of Baseball’s Greatest Players. He ranked second, behind only Warren Spahn, among left-handed pitchers. That same year, Grove was elected to the Major League Baseball All-Century Team. In the 2001 book The New Bill James Historical Baseball Abstract, Bill James ranked Grove as the 19th best baseball player of all time and the second-best MLB pitcher of all time.

The objective of the Lefty Grove Memorial Committee is to preserve the memory of Grove. The Lefty Grove Memorial committee is based in Grove’s hometown of Lonaconing, Maryland. The memorial was completed and opened to the public on June 22, 2019.