The simultaneous showings around the globe will be anchored by a star-studded premiere at the Nokia Theatre, a 7,100-seat concert venue across the street from Staples Center, where many of Jackson's rehearsals - and his high-profile public memorial - were held.
Longtime Jackson collaborator Kenny Ortega, who directed and produced "This Is It," is expected to attend, as are members of Jackson's band and the executors of his will. Entertainers including Snoop Dogg, Smokey Robinson and Zac Efron are also on the guest list.
Fans are likely to swarm the area, too: Many waited in line for days to buy tickets for advance screenings of "This Is It" at the new Regal Cinemas on site, which will show the film to sold-out audiences Tuesday on all 14 of its screens.
The film, culled from more than 100 hours of rehearsal footage, shows an enthusiastic King of Pop meticulously crafting his moves and performing some of his most beloved hits. No critics have seen it, but Sony - which paid $60 million for the film rights - showed a 12-minute clip to entertainment journalists last week.
Some of Jackson's family members and friends have seen "This Is It" in its entirety. Elizabeth Taylor, a longtime friend of the pop star, posted her thoughts Monday on Twitter.
"It is the single most brilliant piece of filmmaking I have ever seen," she wrote on the micro-blogging site. "It cements forever Michael's genius in every aspect of creativity."
The 77-year-old actress added that she "wept from pure joy at his God-given gift" and urged her fans to see the film "again and again."
"This Is It" opens in theaters Wednesday for a limited run, lending it some of the exclusivity of Jackson's aborted concert stand in London.
"We think the 16 days is right. It's sort of a special event that you want to frame in a special way," said Rory Bruer, head of distribution for Sony.
Jackson died June 25 at age 50. The Los Angeles County coroner has ruled the death a homicide, caused primarily by the powerful anesthetic propofol and another sedative. Jackson's personal physician, Dr. Conrad Murray, has not been charged with a crime but is the focus of the police investigation.
Jackson's 50 comeback concerts at London's O2 arena were to have begun in July.