Signed by the New York Knicks in 1946, just after World War II, he spent four seasons playing as a professional player. The New York Knicks were a member of the Basketball Association of America (BAA), which merged into the National Basketball Association (NBA) in 1949. In the four years (1946–50) he played in the BAA and the NBA, van Breda Kolff turned in a relatively unimpressive performance, shooting just .305 from the field, .669 from the line, and averaging 4.7 points in 175 contests. He was also elected team captain of the Knicks.
Van Breda Kolff also spent time running a women’s professional team and later coached a high school team in Picayune, Mississippi. “Coaching is coaching,” he once told a reporter. “Give me 10 players who want to work and learn the game and I’m happy. I don’t count the house.”
Van Breda Kolff's success in college attracted the attention of the NBA. The Lakers hired him in 1967, and in his first season guided the team to the NBA Finals, where they lost to the Boston Celtics in six games. In his second campaign there, his team—with Elgin Baylor, Jerry West, and Wilt Chamberlain—notched a 55-27 record and reached the Finals again. Van Breda Kolff took tremendous flak for not allowing Chamberlain (with whom the coach feuded all season), back in the game for the final minutes of game 7 of the NBA finals against Boston. Chamberlain picked up his 5th foul midway through the 4th quarter, and shortly thereafter asked out of the game with knee pain (this was the same knee Chamberlain severely injured at the beginning of the following season). With backup center Mel Counts in the game, the Lakers cut a double digit deficit to two points. Chamberlain then motioned to Van Breda Kolff that he was ready to go back in the game, to which Van Breda Kolff told him "sit your big ass down." The Lakers lost by two points, and van Breda Kolff resigned shortly afterward.
He then went on to Detroit, where he coached the Pistons for just over two seasons. In 1970–71 he guided the team to a 45-37 mark, Detroit’s first winning season in 15 years. He left the team 10 games into the next season. Van Breda Kolff coached the Phoenix Suns for the first seven games of the 1972–73 campaign before being fired and replaced by Jerry Colangelo, then did a stint with Memphis of the American Basketball Association in 1973–74. From 1974 to 1977 he coached the New Orleans Jazz, taking over in the middle of the 1974–75 season and departing with a 14-12 record partway through the 1976–77 season.
While he was coach, he pushed for New Orleans to relinquish the rights to Moses Malone in exchange for a #1 draft pick, and then traded that pick and two other #1s to the Lakers for Gail Goodrich. This turned out to be one of the worst decisions in NBA history, not only because Malone became a superstar but because Goodrich suffered an Achilles' tendon injury that would end his career in 1978. The Jazz's #1 pick in 1979 (the first overall choice) was used by the Lakers to select Magic Johnson.
While in New Orleans, he also coached the New Orleans Pride, a women’s professional squad. He left the professional ranks for good in 1976, taking with him a career NBA coaching record of 266-253 and a .513 winning percentage. 1976 also marked the year his son Jan entered the NBA with the New York Nets; he coached one game against his son's team.
Van Breda Kolff often clashed with other strong egos. After leaving the Jazz, he remained in New Orleans and returned to the college coaching ranks with the University of New Orleans, where he spent two years. In 1985, Lafayette, the team he had coached 30 years earlier, asked him to return. Van Breda Kolff stayed four seasons at Lafayette before leaving to coach Hofstra once again. His second stint with the Flying Dutchmen lasted five seasons and ended after the 1993–94 season. In 28 years as a college coach, he compiled a 482-272 record.
“All I know is life isn’t much different than that game on the court,” he said in an article in the New York Daily News in the early 1980s. “If it’s run right—with precision, with good, honest effort—it’s a thing of beauty. I know what it looks like and that’s what keeps me going.”