Newble signed as a free agent with the NBA's San Antonio Spurs and his NBA debut with in the 2000–2001 season, playing in 27 games, of which he started six. In just under seven minutes per game, he averaged 2.0 points per game and 1.3 rebounds per game. He was waived by the Spurs after the season. He then signed with the Atlanta Hawks for the 2001–2002 season, and his playing time and production greatly increased. Playing 42 games, he played over 30 minutes per game, averaging 8.0 ppg and 5.3 rpg, which would both be career highs for Newble. On April 13, 2002 against the Cleveland Cavaliers, Newble set a then career single-game high with 17 points and a career-high 12 rebounds. The following season, 2002–03, he played in 73 games, averaging 7.7 ppg, 3.7 rpg, and a career-high 1.4 assists per game. On April 12, 2003, he set a career personal-best with 21 points against the Washington Wizards, then topped that two days later with 23 against the Orlando Magic. The Cleveland Cavaliers signed Newble as a free agent in July 2003. In the 2003–04 season, in 64 games playing about 19 minutes per game, he averaged 4.0 ppg and 2.4 rpg. In 2004–05, he played a career-high 74 games, averaging 5.9 ppg and 3.0 rpg. Injuries hampered Newble in the 2005–06 NBA season. He missed 21 games with a right foot strain and missed 14 games with a facial abscess, limiting him to 36 games. In 2006–07, he was limited to only 15 games. In 2007–08, he bounced back, playing in 41 games for the Cavs then, on February 21, 2008, he was traded to the Seattle SuperSonics in a multi-player deal. He was waived by the Sonics one week later after playing just two games. In the 2006–07 NBA season he was a part of the team that won the Eastern Conference Championship. In March, 2008, Newble signed a 10-day contract with the Los Angeles Lakers. Nine days later, the Lakers signed Newble for the remainder of the season. He played six games for the Lakers, ending his eight-year NBA career with 1,930 points, 1,114 rebounds, 342 assists, 204 steals and 105 blocks in 380 games.
In 2011, Newble became an assistant coach of the Canton Charge, the new NBA Development League affiliate of Newble's former team Cleveland Cavaliers. In 2012, Newble became an assistant coach for the Austin Toros of the NBA Development League. He would continue to coach for the Toros under their last two seasons in that name before being renamed to the Austin Spurs. On October 31, 2015, he became an assistant coach for the Bakersfield Jam.
Ira Newble leads a campaign to help bring awareness to China's involvement in the Darfur crisis. Ira Newble saw a letter that Aid Still Required had written expressing concern about investments funding the crisis in Darfur. He collected signatures around the league for the letter that then was presented to the Chinese Government and the President of the Olympic Committee for the 2008 Summer Olympic Games.
