In the fall of 1960, Boozer joined the Royals with Olympic teammate Oscar Robertson. As a rookie, Boozer contributed 8.4 points and 6.2 rebounds in a reserve role. The following season, he earned a spot in the Royals’ starting lineup and averaged 13.7 points and 10.2 rebounds. Boozer continued to improve, averaging 14.3 points and 11.1 rebounds during the 1962–1963 season, but the emergence of forward Jerry Lucas, a future Hall-of-Famer, soon pushed Boozer out of the Royals' long-term plans. Boozer's contract was sold to the New York Knicks in the middle of the 1963–64 season, and he spent the next 1½ seasons in New York. Though Boozer was a productive player with the Knicks, he was traded to the Los Angeles Lakers in 1965.
After one season in Los Angeles, where he played a supporting role amid players like Jerry West and Elgin Baylor, Boozer was selected by the Chicago Bulls in the 1966 NBA Expansion draft. Boozer flourished in his first year with Chicago, averaging 18.0 points and 8.5 rebounds and leading the young franchise into the playoffs. The following year, he averaged 21.5 points and 9.8 rebounds and became the third Bull to appear in the NBA All-Star Game (after Guy Rodgers and Jerry Sloan). During the 1968–1969 season, Boozer averaged a career-high 21.7 points per game, but the Bulls failed to make the playoffs, and Boozer was soon traded to the Seattle SuperSonics. He spent one productive season with the Sonics and then joined the Milwaukee Bucks and won an NBA championship with the team in 1971. He retired after that season. He ended his career with 12,964 total points and 7,119 total rebounds.
Boozer returned to Omaha after his career ended, and worked as an executive for the Bell Systems. He was later appointed to the Nebraska Parole Board and volunteered at Boys Town, the home for troubled youth.
Bob Boozer Drive is a street named in his honor in his native Omaha.
Boozer died due to a brain aneurysm in Omaha, Nebraska on May 19, 2012. He was 75.