He began his major-league career in 1961. From the beginning, there was tremendous pressure on him to perform, as he succeeded to the position of Sox legend Ted Williams. He would prove to be a worthy successor at the plate, and a far superior defensive player. While his first two years were viewed as solid but unspectacular, he emerged as a rising star in 1963, winning the American League batting championship with a batting average of .321, and also leading the league in doubles and walks, finishing sixth in the Most Valuable Player voting.
Yastrzemski enjoyed his best season in 1967, when he won the American League Triple Crown with a .326 batting average, 44 home runs (tied with Harmon Killebrew) and 121 RBIs. He is the last hitter to have won the Triple Crown as of the 2007 season (six different pitchers have since won the pitchers' version). He was voted Most Valuable Player almost unanimously (one voter chose César Tovar of the Twins).
1967 was the season of the "Impossible Dream" for the Red Sox (referring to the hit song from the musical play Man of La Mancha), who rebounded from a ninth-place finish a year before to win the American League pennant (their first since 1946) on the last day of the season. With the Red Sox battling as part of a four-team pennant race, Yastrzemski collected 13 hits in 21 at bats (a .619 batting average) over the last six games of the season, and finished a mere one game ahead of the Detroit Tigers and Minnesota Twins. The Red Sox lost the World Series four games to three to the St. Louis Cardinals, losing three times to Bob Gibson. In that season, Yastrzemski also won the Hickok Belt as top professional athlete of the year and Sports Illustrated magazine's "Sportsman of the Year" Award.
In an article he co-wrote for the November 1967 issue of SPORT magazine, Yastrzesmki credited the Red Sox remarkable season to manager Dick Williams and an infusion of youth, including Rico Petrocelli and Tony Conigliaro. Referring to Williams, Yastrzemski wrote: "He got rid of all the individuality, made us into a team, gave us an incentive, and made us want to win."
In 1968 Yastrzemski again won the batting championship. Because of the competitive advantages pitchers enjoyed between 1963 and 1968 (prior to the lowering of the pitcher's mound), Yastrzemski's .301 mark in "The Year of the Pitcher" is the lowest average of any batting champion in major league history; however, he was the only hitter in the American League to hit .300 for that season against such formidable pitching, as well as leading the league in on-base percentage and walks. He had many more strong seasons, consistently finishing in the top ten in the league in many statistical categories.
In 1969, he hit the first of 2 straight 40 home run seasons as he led the Red Sox to third-place finishes that year and the next. Yaz got four hits and won the All-Star Game MVP in 1970, although the American League lost. His .329 batting average that season was his career high, but finished behind Alex Johnson for the 1970
Although he hit but 61 homers over the next four years (1971 through 1974) as the Red Sox finished second twice and third twice, he finished in the top 10 in batting, and top three in on base percentage and walks in 1973 and 1974, and led the league in runs scored in 1974.
Yastrzemski and the Boston Red Sox would suffer another World Series loss in 1975, losing four games to three to the Cincinnati Reds. Yaz made the final out in Game 7 on a fly out to center, trailing by one run. Coincidentally, he also made the final out of the 1978 American League East division one-game playoff with a foul pop to third base. This game featured Bucky Dent's famous homer (although Reggie Jackson's home run was the eventual winning run). Earlier in the game, however, Yastrzemski began the scoring with a home run off left handed pitcher Ron Guidry, who was having a career year (25 wins, 3 loses and a 1.74 ERA). It was the only homer the Cy Young Award winner allowed to a left-hander all season. in 1978 Yastrzemski was the second oldest player in baseball (behind Jim Kaat).