It happened around 8:45 p.m. Monday on New Schuylkill Road (Route 724), near Sanatoga Road, in East Coventry Township.
Police say a 2005 Honda SUV carrying six teenage boys veered into the eastbound lane, hit an embankment and rolled over.
The SUV then hit a Nissan coming in the opposite direction.
Two of the boys in the SUV were killed after they were ejected from the SUV. They have been identified as Pottsgrove High School students Andrew Case and Mike Cantamaglia.
Four other boys in the SUV and a woman who was driving the Nissan were all taken to Reading Hospital.
The accident remains under investigation.
Students grieving their loss
Though Pottsgrove was closed for the holiday, grief counselors and teachers were there on Tuesday to offer solace to students in mourning.
"Any time there's children involved in a tragedy like this... it just really touches the heart strings, particularly at the holiday season," said superintendent Brad Landis.
Word of the accident spread quickly through the Pottsgrove community.
"I'm really upset about it," said Pottsgrove senior Josh Lucas. "Everybody's upset about it."
Practice and other activities were cancelled at the school.
"I think everybody's going to be talking about it and everybody's going to mourn them and be sad for them," said sophomore Charles Wildonger. "But when school starts again it's going to be way different."
Pottsgrove High School will remain open through Tuesday night for anyone who may need to talk to a grief counselor.