His Oregon Project teammate, Matthew Centrowitz, has withdrawn from the race.
The 17-year-old Cain took nearly a second off the previous mark.
The American runner shared his life story last week.
The Americans bring a strong field to this year's race in the heart of Manhattan.
The 17-year-old finished second in the women's 1,500m final at the U.S. Championships.
Most of the pre-meet contenders advanced through the preliminary rounds.
The Sudan native came to the U.S. in 2001 as one of the "Lost Boys."
All seven starters set an indoor personal best.
The U.S. Olympian moved to New York from South Sudan in 2001.