Runnels was born in Lufkin, Texas. A master at handling the bat, he was a notorious singles hitter who had one of the best eyes in the game, compiling an outstanding 1.35 walk-to-strikeout ratio (844-to-627). Altogheter he batted over .300 six times, once with the Senators, five with the Red Sox.

Solid and versatile with the glove, Runnels started as a shortstop with the Senators, but ultimately played 644 games at first base, 642 at second, 463 at shortstop, and 49 at third. Twice he led the American League in fielding percentage, at second base in 1960 (.986) and at first base in 1961 (.995).

In five seasons with Boston Runnels never hits less than .314 (1959), winning two batting crowns in 1960 (.320) and 1962 (.326), and just missed one by six points with his teammate Ted Williams on the final day of the 1958 season (.328 to .322). That year, Runnels also set career-highs in home runs (10) total bases (256) and slugging percentage (.456), was considered for the MVP award (10th), and won the Comeback Player of Year award (batting average went from .230 to .322) .

On August 30, 1960, in a double-header against the Tigers, Runnels hit 6-for-7 in the first game (including a game-winning RBI-double in the 15th inning) and 3-for-4 in the second, tying a Major League record for hits in a double-header (11). After winning his batting title in 1962, Runnels was traded to the Houston Colt .45s (forerunners of the Astros). He gave them two years of good services, retiring at the end of the 1964 season.

Runnels was a career .291 hitter (1854-for-6373) with 49 home runs, 630 RBI, 876 runs, 282 doubles, 64 triples, 37 stolen bases, and a .375 on base percentage in 1799 games. He was selected an All-Star in 1959, 1960 and 1962, and he also coached for the Red Sox in 1966, serving as an interim manager for the last 16 games.

Pete Runnels died in Pasadena, Texas, at the age of 63. He was inducted to the Boston Red Sox Hall of Fame in November 2004.