The news confirms a Polygon report from late April, based on a source close to NBA 2K16 as well as leaked marketing materials.
Lee told the AP that NBA 2K16's campaign centers on a fictional player named Frequency Vibrations, and tells a story of "the trials and tribulations of life on a big stage with the money, fame, temptations, family members, the press, fans, all that stuff."
Both Lee and 2K Sports said it didn't take much convincing for the director to come on board.
"Spike was really receptive when I first met with him," said Jeff Thomas, vice president of sports development at Visual Concepts, the studio behind NBA 2K. "He actually said to us, 'It's about time I worked with 2K.' He loves basketball, and this is a new frontier for him."
Lee is a die-hard New York Knicks fan, and directed the 1998 basketball film He Got Game. While most of his films are R-rated productions, 2K Sports said that NBA 2K16's career mode will fit the series' ESRB rating of E for Everyone.
The AP also reported that NBA 2K16 will come in three different covers featuring Stephen Curry of the Golden State Warriors, James Harden of the Houston Rockets and Anthony Davis of the New Orleans Pelicans. Polygon reported in April that marketing plans called for three different covers, involving Curry, Harden and NBA 2K15 cover star Kevin Durant.
NBA 2K16 will be released Sept. 29 on PlayStation 3, PlayStation 4, Windows PC, Xbox 360 and Xbox One. Those who pre-order the game will receive it Sept. 25, four days ahead of the public release.
Update: You can see all three NBA 2K16 covers below. 2K Sports confirmed in a press release June 5 that buyers of the game will be able to put whichever cover they like on the box.
"While game covers will be distributed at random, fans can rest at ease knowing that each game box includes a foldable insert with all 3 individual cover athletes, ensuring the ability to insert the cover of their choice into the front of box," reads the press release.
2K Sports also released an extended version of a commercial for the game featuring Spike Lee; the original aired on the night of June 4, prior to Game 1 of the NBA Finals. The video is below.