James, who entered the game needing nine points to reach the milestone, used a spin move to create separation from Denver's Michael Porter Jr. and put the ball in with his left hand as the all-time scoring leader continues to put his record further out of reach.
The sold-out crowd in downtown Los Angeles roared with approval when James made the highly-anticipated shot to reach 40,000 points and gave him a standing ovation when he went to the bench at the next break.
The four-time champion "King James" became the league's scoring king just over a year ago when he passed Lakers great Kareem Abdul-Jabbar.
The 39-year-old is the oldest player in the NBA, but continues to produce at an elite level in his 21st season, where he is on track to average about 25 points per game.
On Wednesday, James scored 19 points in the fourth quarter to overcome a 21-point deficit to the Clippers as the 10th-placed Lakers fight for a playoff spot in the crowded Western Conference.
Drafted into the league as a teenager, the Akron, Ohio native has more than delivered on the massive expectations put on his broad shoulders at a young age.
A versatile forward, he helped usher in the era of position-less basketball, winning four titles with three different teams, four MVP awards and four Finals MVP awards.
James has a player-option for the 2024-25 NBA season, which gives him the power to decide whether to stay with the Lakers for another year or become an unrestricted free agent. So far, he has refrained from committing to the Lakers beyond the current season.
In January, James was among the 41 names listed in USA Basketball's player pool for the Paris Olympics. He has not played for Team USA since he won a gold medal at the 2012 London Olympics.
