Born in Beach Haven, New Jersey, Cramer was an elegant center fielder with speed and a powerful arm. He was nicknamed "Flit", which was the name of a popular insecticide, by sportswriter Jimmy Isaminger for his great ability to judge fly balls; in other words, because he was "death to flies" (he led the league in putouts in 1936 and 1938).

He began his career with the Athletics' powerful championship teams of 1929-1931, breaking in gradually, though in the postseason he only made two pinch-hitting appearances in the 1931 World Series. He tied a major league record by going 6-for-6 in a nine-inning game, and became the only AL player to do it twice (June 20, 1932 and July 13, 1935); he also hit for the cycle on June 10, 1934. After hitting .336 in 92 games in 1932, his place was secure, and he scored 100 runs for the first time in 1933; but the team's fortunes declined simultaneously, leading to the star players on the financially struggling Athletics being sent to other teams. Al Simmons and Jimmy Dykes were sold to the Chicago White Sox on the same day in September 1932, and Lefty Grove and Mickey Cochrane were traded away after the 1933 season. In 1934 Cramer set a team record among left-handed hitters with 202 hits, and topped it in 1935 with 214 - still the Athletics franchise record for a left-handed batter; he finished eighth in the 1935 MVP voting. Afterwards, Jimmie Foxx was traded to the Red Sox in December 1935, and Cramer joined him a month later.

Cramer was a spray leadoff hitter who used raw speed to get on base and to stretch singles into doubles. He batted over .300 every year from 1937 to 1940 with Boston, scoring 100 runs in 1938 and 1939, and tied for the league lead in hits (200) in 1940. He was traded to the Washington Senators on December 12 of that year, and was sent to the Detroit Tigers exactly one year later after hitting .273. He was selected for the All-Star game five times (1935, 1937-40).

Two years after hitting over .300 for the last time with the 1943 Tigers, in 1945 Cramer played 140 games in center field at age 40, and finally enjoyed significant play in the Fall Classic. In the 1945 World Series he led the team with a .379 batting average, scoring seven runs and batting in four, to help his team to win the Series 4-3 against the Chicago Cubs; he had two runs and an RBI in Game 5, and again in Game 7. In his final seasons he was often used as a pinch-hitter, and he led the league with nine pinch hits in 1947 before ending his career with four games in 1948. His 2031 games in center field placed him behind only Tris Speaker (2690) and Ty Cobb (2194) in major league history. Later, as a White Sox batting coach, he tutored the young second baseman Nellie Fox from 1951 to 1953; frequently, Fox credited Cramer with making him a major league hitter.

In his 20-season career, Cramer batted .296 with 2705 hits, 1357 runs, 37 home runs, 842 RBI, 396 doubles, 109 triples, 62 stolen bases, and a .340 on base percentage in 2239 games. By team, he batted .308 for the Athletics, .302 for the Red Sox, .282 for the Tigers, and .273 for the Senators. His 2705 hits are the most of any player retired before 1975 who has not been elected to the Baseball Hall of Fame.

Cramer's case for the Hall of Fame is weak on the basis of hitting alone. His lifetime batting average of .296 is only a bit better than the .283 overall average of all the players against whom he competed in a "high-average" era. He also did not walk much, so his lifetime on-base percentage of .340 ends up being lower than the .357 overall average of all the players against whom he competed. His lack of walks and his utter lack of speed on the basepaths -- 62 stolen bases for his entire career (against 73 times caught stealing) -- are big drawbacks for a batter who hits at the top of the order. Given that Cramer had no power, either, he was significantly below average as an offensive force.

Cramer's fielding statistics support the common belief that he was a fine glove man. His lifetime fielding percentage and range factor well exceed league averages for his time. Of course, very few if any outfielders have been selected to the Hall of Fame primarily for great fielding ability.

Cramer died in Manahawkin, New Jersey at 85 years of age. There is a street named in his honor: Doc Cramer Blvd.