Garciaparra was part of the so-called "Holy Trinity" of shortstops that debuted in the mid '90s, which also included Alex Rodriguez (now a third baseman) and Derek Jeter, who were considered the best shortstops in baseball.

Garciaparra, whose middle name is the reverse of his father's name "Ramon", was a first round pick of the Red Sox in 1994 following a successful career at Georgia Tech. At the time, Boston's starting shortstop was John Valentin, who finished ninth in MVP voting in 1995. But by late 1996, Nomar won the job. Garciaparra's talent was enough to displace Valentin, who was moved to second base (then third base) to make room for young Garciaparra, who batted .241 with 4 home runs, 16 RBI, and 5 stolen bases in his initial stint with the club, near the end of 1996. As a rookie in 1997, he hit 30 home runs and drove in 98 runs, setting a new MLB record for RBIs by a leadoff hitter. He was named Rookie of the Year in a unanimous vote, competed in the Home Run Derby, and finished eighth in MVP voting. He also won the immediate admiration of Red Sox fans, who referred to him in Boston accents as "Nomahh". With his hard work and idiosyncratic quirks, his popularity easily stretched well beyond Red Sox Nation.

From 1998-2000, Garciaparra emerged as the best hitter of the Holy Trinity of shortstops, with the highest career OPS of the three by the conclusion of this period. He finished with 35 home runs and 122 RBI in 1998, and placed as the runner-up for AL MVP. Garciaparra then led the American League in batting average for the next two years, hitting .357 in 1999 and .372 in 2000, finishing in the top ten in MVP voting both years. He is one of the few right-handed batters to win consecutive batting titles.

In February of 2001, Garciaparra appeared on the cover of Sports Illustrated, with the headline "A Cut Above... baseball's toughest out". The week after the issue hit newsstands, Garciaparra reported to spring training with a serious wrist injury, which essentially aborted his season. He recovered by the start of the 2002 season and drove in 120 runs while hitting a league-leading 56 doubles. However, he had a difficult time playing as strongly defensively as before, and his batting average dipped substantially.

Before the 2002 season, a new ownership group purchased the Red Sox. The baseball operations staff, led by Theo Epstein, stressed on-base percentage on offense and strong defense, the two areas where Garciaparra was about to decline precipitously from his pre-2001 levels. Nomar was also up for a contract extension as the 2003 season approached, and found the Red Sox unwilling to approach the excessive salaries paid to his peers Rodriguez and Jeter by the Texas Rangers and New York Yankees, respectively. Garciaparra's 120 RBIs in 2002 masked declining rate statistics across the board that alarmed Red Sox management.

In 2003, Garciaparra ended a solid but unspectacular season with a miserable September, closing with a career-low .301 batting average. He then followed that with a poor post-season, contributing zero home runs, one RBI and ten strikeouts in 12 games vs. the Oakland Athletics and rival Yankees, who eliminated the Red Sox in seven games.

Meanwhile, new stars and cult heroes, led by David Ortiz and Kevin Millar, began to emerge. Millar coined the catch phrase "Cowboy Up" in 2003, and convinced nearly every player on the roster other than Garciaparra to shave his head. For his part, Garciaparra became more reclusive and isolated as his star slowly faded in the new, more team-oriented era of Red Sox baseball. What was once idiosyncratic and "cool" about Nomar now felt bitter and self-involved in the changing context of the Epstein-era Red Sox. To a similar extent, the demise of Boston's star culture for a populist approach also alienated pitcher Pedro Martinez, another holdover from the late '90s Dan Duquette regime which encouraged a different set of standards for star players, particularly Martinez and Garciaparra.

After the 2003 season, Red Sox management sensed an opportunity and, with contract negotiations at a standstill, traded Garciaparra as part of a mega-deal to acquire Alex Rodriguez prior to the 2004 season. The deal fell apart when the MLBPA refused to approve a restructuring of Rodriguez's contract, and Garciaparra returned to Boston as a lame duck for 2004 in the final year of a contract he signed in 1997.

2004 saw Garciaparra claim to have suffered an injured Achilles' tendon when a foul ball hit him in spring training, an incident no one could corraborate that cost him nearly three months of playing time. When he did return, Garciaparra made two errors in the first two games of a series with the rival Yankees, then asked out of the lineup during a 13-inning loss to the Yankees on July 1 that saw friendly nemesis Derek Jeter dive headfirst into the stands for a foul ball as Garciaparra sat alone, apparently pouting, in the Red Sox dugout, a moment widely felt to be the final nail in Garciaparra's coffin in Boston. Four weeks later, he asked out of the lineup in Minnesota one day before the trading deadline, citing the same injury. When the training staff could not detect the problem, Red Sox management acted.

On July 31, 2004, at the MLB trading deadline, Garciaparra was traded from the Red Sox to the Chicago Cubs in a four-way deal, in which the Red Sox acquired Orlando Cabrera and Doug Mientkiewicz. He expressed his appreciation to Red Sox Nation in a speech to media and left for the Windy City. It is worth noting that though many in Boston felt Garciaparra was faking his injury, he went on the disabled list for the Cubs with a strained Achilles' tendon in August of 2004.

In the 2005 season, a torn left groin forced him onto the disabled list yet again for more than three months. Garciaparra resumed play on August 5, 2005. Because Cubs regular third baseman Aramis Ramírez was on the disabled list for the last few weeks of the 2005 season, he temporarily played third base. Aside from his first game in the majors, in which he played second base, he had played shortstop in all of his other major-league games up to that point in his career.