O'Neal finished with 20 points, giving him 25,015 in his career, as Miami fell to 1-2 without top scorer Dwyane Wade, out with a dislocated shoulder.
O'Neal is the top scorer among active players and 14th overall in NBA history. The center is the seventh to reach 25,000 points and 10,000 rebounds. Next up on the list is Lakers great Jerry West in 13th place with 25,192.
The milestone basket came with 6:04 left in the period when he muscled Knicks forward Malik Rose in the paint, backed him up and then scored over him to give Miami a 16-9 advantage. O'Neal had an earlier scoring drive and a thunderous dunk
The 15-year NBA veteran is the first to hit the scoring milestone since Indiana's Reggie Miller on March 23, 2005. O'Neal, limited to just 17 of Miami's first 56 games this season because of a knee injury, came in with 11,193 rebounds.
He joins Kareem Abdul-Jabbar, Karl Malone, Wilt Chamberlain, Moses Malone, Elvin Hayes, and Hakeem Olajuwon as those with 25,000 points and 10,000 rebounds.
The Heat are counting on O'Neal to carry them down the stretch while leading scorer Dwyane Wade is sidelined because of a dislocated left shoulder. Miami went 18-21 without O'Neal this season.
Wade is expected to join the team at the White House on Tuesday, when they are honored for winning last season's NBA championship, and then visit a doctor the following day to get another opinion on his shoulder.