Octavio Chavez-Renovato, 45, of Chicago, his wife, Eva Gonzales, 34, who was in the passenger seat, and their son, Luis, 14, were killed. The couple's three young daughters survived, but were seriously injured.
Emergency crews responded to the crash about 1:40 a.m. in the eastbound lanes of the Indiana Toll Road near the Grant Street exit in Gary, according to Indiana State Police.
A Toyota SUV was being driven west in the eastbound lanes without its headlights on, police said. It collided head-on with the family's Jeep SUV which had been traveling in the left lane.
"Initially I didn't think there was anyone who made it through that," said witness Donte Moffett, who along with his wife, China Leatherwood, pulled over to aid the victims.
The driver of the Toyota, identified by a family member as Tiara Davis, 25, of Calumet City, was pronounced dead at the scene by the Lake County Coroner, police said.
Indiana State Police said Davis was driving for nearly seven miles before colliding with the Jeep.
"I opened the door and saw a baby," said Leatherwood. "I took the baby out and handed it to my husband. There was another girl, just 'help, help' and he and I pulled the girl out. But once we pulled the girl out we realized there were two more kids in there. And they were moving."
A licensed practical nurse, Leatherwood says she tried to administer as much aid as she could. But ultimately the mother died in her arms. Her son following a few minutes later.
"The boy was breathing at first. He kept looking at us and I kept saying, 'breath baby, breathe.' Him and other truckers helped get the mother out. Once they got her out I checked the heartbeat and it was very faint. He stayed with the little boy and I tried CPR with the mom."
Three other children in the Jeep - the family's daughters, Damaris, 11; Emily, 10; and Florali, 7 months - were seriously injured and initially taken to Methodist Hospital in Gary, according to police. Emily was later air-lifted to Advocate Christ Medical Center, while Damaris and Florali, the latter in a child safety seat, were flown to Comer Children's Hospital.
Police believed alcohol may have been a factor in the crash. Toxicology was pending.
Sun-Time Media Wire contributed to this report.