Giles was born in El Cajon, California, and attended Granite Hills High School. He was drafted by the Cleveland Indians in the 17th round of the 1989 Major League Baseball draft. By 1994, Giles had worked his way up to Triple-A, where he batted .313 for Charlotte making the International League All-Star team. In 1995, Giles was again in Triple-A, where he batted .310 for Buffalo and made his major league debut as a September callup on September 16 (where he would bat .556 in nine at-bats with the Indians). He was also an American Association All-Star. Giles hit .355 in 51 games for the Indians in 1996 and hit .314 in 83 games with Buffalo, again making the American Association All-Star team. In 1997, Giles established himself as a major league regular, playing 130 games for the Indians and 112 games in 1998.

On November 18, 1998, he was traded to the Pittsburgh Pirates for pitcher Ricardo Rincón.

In 1999 with the Pirates, Giles emerged as a power-hitting outfielder who also hit for average and showed plate discipline. He began a streak of hitting at least 35 home runs for four straight seasons, during which he batted no lower than .298 and was named Pittsburgh Pirates Player of the Year each year.

In 2001 Giles established career highs in games played, at bats, runs and hits. He tied career highs in doubles, triples and stolen bases. At the end of the season he ranked tenth among N.L. players in runs, on-base percentage, .404, and slugging percentage, .590. His 116 runs scored were the most by a Pirate since Ralph Kiner in 1951. He led the Pirates in batting, home runs and walks. He tied Dave Parker’s club record for most total bases, 340, by a left-handed hitter. Giles hit his 100th career home run as a member of the Pirates on August 9, he is one of 17 players to homer 100 times as a Pirate. He was selected to play in the All- Star Game for the second consecutive year.

Giles ranked second in the league in walks behind San Francisco’s Barry Bonds, who led with 198 in 2002. He also established the club record for most base on balls in a season by a left-handed batter. His .450 on-base percentage tied him for the second-best mark in the majors, he also ranked second in the league in slugging percentage with .622, sixth in home runs, second with 80 extra-base hits ranked second behind San Francisco’s Jeff Kent, tied for second in the league with 13 outfield assists and also finished third in the N.L. with 24 intentional walks. He homered once every 13.1 at bats, the third-best ratio in the league behind Bonds’ 8.8 and Sammy Sosa’s 11.3.

Giles was sued by his former girlfriend for more than $10 million. She alleged Giles broke an oral and/or implied agreement that he would take care of her for an indefinite period of time. She alleged Giles began abusing her in 2002, and battered her while she was pregnant with Giles’ child, and caused her to have a miscarriage. She dropped the allegations that Giles caused the miscarriage before the trial began. A jury found that both Giles and his girlfriend, Cheri Olvera, committed acts of domestic violence against each other but that there were no damages. The jury also refused to award damages on Olvera’s contract claim, finding that Olvera’s alleged terms were not clear enough so that both Olvera and Giles could understand what each was required to do. Instead, the jury found that Olvera must return the $107,000 engagement ring Giles provided to her or pay the $107,000 as damages. Following Giles’ dispute with Olvera and given the nature of the court case, Giles’ endorsement contract with Nair Hair Removal products was terminated.

On August 26, 2003, he was traded to his hometown San Diego Padres for Jason Bay, Óliver Pérez, and minor leaguer Corey Stewart.

From 2004–2006, Giles played in over 150 games each season for the Padres, but in 2006, his batting average dropped to a career-low .263. On May 14, 2006, he drew five walks in a game, one shy of the record of six. In 2007, joined by his brother Marcus, signed as a free agent to be the starting second baseman, Giles batted .271, but missed time with an injured knee.

In 2008, Giles, in the third and final guaranteed year of his contract with the Padres, vetoed a potential trade to Boston, citing a desire to remain close to his family In 2008, 58% of his strikeouts were “looking”, by far the highest percentage in the major leagues.[3]

In 2009, through July 1 Giles had the lowest batting average (.191), slugging percentage (.271), and OPS (.548) in the major leagues.[4] However, he went on the disabled list soon afterward with an arthritic right knee and missed the rest of the season.

On February 7, 2010, Giles signed a minor league contract with the Los Angeles Dodgers and received an invitation to spring training. However, after playing in just two spring training games as a designated hitter, he announced his retirement on March 11, 2010.