Miles attended East St. Louis High School, and, after failing to receive a qualifying SAT score to attend St. John's University, entered the 2000 NBA Draft and was selected by the Los Angeles Clippers as the third overall pick, making him the highest-drafted high school player ever at that time. For the next 2 NBthe seasons, Miles, a Six' Ennead", 210 pound (95 kg) small forward, formed, along with Lamar Odom, Quentin Richardson, and Elton Brand, the core of a young Clippers team that became popular among young basketball fans for their exciting, high-flying style of play. Prior to the 2002-03 season, he was traded to the Cleveland Cavaliers. The Cavaliers had a disastrous 17-65 season, with Miles' own futility being the target of much media criticism. Luckily, the Cavaliers, with the worst record in the league, won the NBA Draft Lottery and were able to select high school phenom LeBron James, a close friend of Miles', with the first pick in the 2003 NBA Draft. With a budding superstar in James, Cleveland no longer need Miles' and traded him to the Portland Trail Blazers midway through the 2003-04 season. While in Portland, Miles began to flash some of the talent that he had started to show with the Clippers before being traded, though most still agree that he has yet to tap into his true abilities. Nevertheless, the Blazers signed him to a six-year, USD$48 million contract extension after the season. During the 2004-05 season, Miles made headlines after a confrontation with then-coach Maurice Cheeks in which he repeatedly insulted hi m and remarked he didn't care if the team were to lose the next 20 games since Cheeks was going to be fired anyway. Though he was suspended two games for his outburst, his statements were prophetic: Cheeks was soon fired, and the team proceeded to lose nearly all of its remaining games.

Miles had a role in the 2004 movie The Perfect Score, as a high school basketball star who needs to achieve a qualifying SAT score to attend St. John's University, closely paralleling his real life situation coming out of high school. Interestingly, he does attend college at the conclusion of the movie, while in real life he chose to skip college and entered the NBA Draft. He also appeared in ''National Lampoon's Van Wilder, along with then-Clipper teammates Michael Olowokandi and Quentin Richardson, in 2002. There was also a documentary titled The Youngest Guns'', which detailed Miles' and Richardson's first few years in the NBA, released in 2004.