Illinois State Police said crash occurred at about 10:36 p.m. near milepost 238 as police said a Ford F-150 was driving north in the southbound lanes near milepost 238 and struck a GMC Yukon head-on. The Yukon was then hit by a semi-trailer.
The driver of the Ford was also transported to a hospital with injuries.
The victims were identified as Kelly and Ron Dube, who had been married for 15 years and had four children between the ages of 2 and 11. They had recently moved into their dream home in rural Emington, about 90 miles southwest of Chicago.
"It was a beautiful family. Four beautiful kids. I love those kids so much. But their parents were just ripped away from them by a senseless act and for the rest of their lives, their lives are completely changed," said Melissa Allen, victim's sister.
Allen said the family had been visiting her in Plainfield and were traveling home after dropping off their eldest daughter for a sleepover.
"They came over just to, like, hang out and we actually brought a side by side back," she said. "My parents have a cabin, so they were coming to pick it up for their kids to be able to ride it and so they were leaving my house later than we expected."
The crash shut down a stretch of southbound I-55 until the early morning hours. The couple was killed instantly, police said. The three children, a 2-year-old boy and 7-year-old twins, were taken to Lurie Children's Hospital in Chicago for treatment.
"Those kids are my first priority. Making sure they are OK. They are taken care of and they have the support that they need just to make it through this," Allen said.
One of the three children was discharged from the hospital Wednesday afternoon, but family said the remaining two will spend at least a couple more days at Lurie.
No charges have yet been filed against the wrong-way driver.