Ken Griffey Jr. was raised in Cincinnati, Ohio, where his father, Ken Griffey, Sr. played for the Cincinnati Reds. The younger Griffey played baseball at Moeller High School, a Catholic school in Cincinnati better known for its football program. While he was in high school, he drew raves from Major League scouts for his batting swing, widely regarded as the best of his generation, and effortless fielding prowess. In fact, Griffey's teammates would supposedly play closer to the lines in order for Griffey to take advantage of (and display) his great range in centerfield.

In 1987 Griffey was selected with the first overall pick of that year's amateur draft by the Seattle Mariners. As a big leaguer, he was well on the way to the Rookie of the Year award but was thwarted when he slipped in the shower and broke a bone in his right hand in late July, 1989. While with the Mariners, Junior, as he is often called, established himself as one of baseball's premier players, and during the '90s, Griffey was considered one of the best players of the time. In fact, many consider him to be the "player of the 90s" despite playing in a hitter's park (the Kingdome) and having arguably inferior statistics to the less-likeable Barry Bonds. Other competitors for the title might have been Frank Thomas and, more questionably, Albert Belle. Before injuries cut into his production, he was a top run producer and the best center fielder in the big leagues although Devon White and Jim Edmonds also merit mention. Griffey hit for a high average, batting over .300 for seven of the years of the '90s, and hit with power as well, slugging 422 home runs during the decade.

Additionally, his defense in center field breeched no rivals during that decade. Thanks to his impressive range, Griffey frequently made spectacular diving plays, and he often dazzled fans by making over-the-shoulder basket catches (a la Willie Mays' "the Catch" in the 1954 World Series) and by robbing opposing hitters of home runs at the wall — leaping up and pulling them back into the field of play. For all of these reasons, Ken Griffey Jr. was one of baseball's most respected and well-liked players during the 1990s. He was featured on the Wheaties cereal box and, because of his general likability and lack of legal problems, was an effective pitchman. Griffey also had his own signature sneaker line from Nike, Inc.

Because of his all-around excellent play, he was a perennial participant in the All-Star Game, particularly during the 1990s although less so during the early '00s because of injuries. Junior has led his league multiple times in hitting categories and was awarded Gold Gloves for his defensive excellence from 1990 to 1999. Griffey also became one of a very small number to have played on the same team as his father, Ken Griffey Sr in 1990 and 1991. In 1997, he won the American League Most Valuable Player award, hitting .304, with 56 home runs and 147 runs batted in.

Perhaps the single most memorable moment of Griffey's career with the Mariners came during the 1995 American League Division Series (ALDS) against the New York Yankees. After falling behind in the series 0-2, they came back to take the next two games and create a must-win Game Five. In the bottom of the 11th inning of Game 5, Griffey scored from first base on an Edgar Martinez double, giving the Mariners the win and seeing them through to the American League Championship Series (ALCS). Although the Mariners lost the ALCS to now-Mariners manager Mike Hargrove's Indians, the moment is one of the most memorable in Mariners history, and the series has been credited with "saving baseball in Seattle", given speculation that the Mariners might move. A video game for Super NES, "Ken Griffey Jr.'s Winning Run" commemorates the moment.

In 1999, he ranked Number 93 on The Sporting News' list of the 100 Greatest Baseball Players. This list was compiled during the 1998 season, counting only statistics through 1997. It was argued by some that, had the voting been done two or three years later, he would have been ranked several places higher: at age 29 (going on 30), he was easily the youngest player on the list. That same year, Griffey was elected to the Major League Baseball All-Century Team. However, when TSN updated their list for a new book in 2005, despite having surpassed 400 and 500 home runs, Griffey remained at Number 93. He is currently 11th place on the all-time home runs list with 554, six ahead of Mike Schmidt and nine behind Reggie Jackson.