The two-time NBA All-Star known as the "Greek Freak" is the first international player to be featured on the cover.
Antetokounmpo said he has "worked hard to earn recognition in the NBA and being on the cover of NBA 2K19 is a dream come true."
He also tweeted that he was "honored" to be the first international player to be on the video game's cover.
"NBA 2K19" will be available Sept. 11.
LeBron James was previously announced as the cover star for the "NBA 2K19" 20th anniversary edition, which will be available on Sept. 7.
The Associated Press contributed to this report.