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 3rd overall pick, at the time the earliest that a player going to the NBA directly from high school had been drafted. For the next two NBA seasons, Miles, a 6' 9", 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 along with Harold Jamison for Andre Miller and Bryant Stith. 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 who also played small forward, Cleveland no longer needed Miles and traded him to the Portland Trail Blazers during through the 2003-04 season in exchange for Jeff McInnis. 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 him with racial slurs (Miles and Cheeks are both black) and remarked he didn't care if the team were to lose the next 20 games since Cheeks was going to be fired anyway. Miles was suspended two games, considered by many to be a lenient punishment, and the team was criticized for not taking a harsher stance on the issue. His statements were prophetic: Cheeks was soon fired, and the team proceeded to lose nearly all of its remaining games.
In the season 2005-06, Miles began the year on a tear. In the first regular season game against the Minnesota Timberwolves, Miles scored 32 points and collected 11 rebounds to go with 5 assists, 5 steals and 3 block shots. He continued the season scoring and grabbing rebounds until he was injured and sidelined for nearly 3 months. He returned in early February with lackluster play. With the trading deadline coming, he upped his playing performance in hopes of finishing his season with a different team. When the deadline passed and he found himself still on the same team and Ruben Patterson shipped out, his desire and motivation to play dropped significantly.
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. His character attends college at the conclusion of the movie. 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.
When Darius makes a basket, he often gestures by pounding his forehead with both fists. This dates back to his Clipper days, when it was devised by him and teammate Richardson.
- Highest high school player selected in 2000 NBA Draft (3rd overall).