The hospital provides comprehensive pediatric specialties and subspecialties to infants, children, teens, and young adults aged 0–21[1][2] throughout Illinois and surrounding regions.

[6] Additionally, Lurie Children's has a rooftop helipad to transport critically ill pediatric patients to the hospital.

[10][11] The site today is home to the DePaul University College of Education building and has a historic plaque at its entrance.

[12] Two years later in 1884, Porter acquired another property a few blocks away from the original building and built a three-story replacement hospital with 22 beds.

[19] By 1908, capacity reached 108 beds after the opening of the "Cribside Pavilion", also allowing admission of infants for the first time in the hospital's history.

[21] In 1926, CMH constructed the new "Martha Wilson Memorial Pavilion", increasing total hospital capacity to 272 beds.

Surgeons Willis J. Potts and Sidney Smith invented a number of surgical tools used to operate on blood vessels and they devised a new surgery to treat blue baby syndrome.

[23] In 1957, it was decided by CMH administration that a new modern hospital building was needed to replace the Maurice Porter and Agnes Wilson pavilions.

[24] Three years later, in 1960 demolition was started and ground was broken to make way for the new patient tower, research building, and administrative offices.

[25] In the 1960s Children's Memorial Hospital's department of anesthesia first established a pediatric intensive care unit (PICU) at CMH with the capacity of 10 beds.

[32] In 2008, the hospital administration and CEO were victims of extortion by then-governor Rod Blagojevich for $8 million of state funding in exchange for a $25,000 fundraiser.

[36] In 2016, demolition on the former Children's Memorial Hospital began to make way for low-rise apartment and retail space.

[41] The new name recognized philanthropist Ann Lurie, and her late husband, in honor of the $100 million gift she made in 2007 to help create the new hospital and to enhance its pediatric research initiatives.

[46] The move was designed to allow the hospital to be closer to its academic partner Northwestern University Feinberg School of Medicine, attract and retain the best staff, foster stronger, collaboration with adult researchers and clinicians, improve transition of patients into adult care, and provide even faster transport for critically ill newborns from neighboring Prentice Women's Hospital.

A local resident organization eventually filed a lawsuit to try and stop the helipad, ultimately losing the case.

[60] In October 2014, the hospital inaugurated its first annual Hope and Courage awards, recognizing "leaders who have demonstrated exceptional commitments to improving the health and well-being of children".

[61] The 2014 honorees were Jamarielle Ransom-Marks, who runs the Jam's Blood and Bone Marrow Drive, child product safety advocates Linda E. Ginzel and Boaz Keysar, and Senator Richard J.

[63] The hospital cited the need for more intensive care beds due to the fact that they were often at capacity, and previously had to turn away patients.

[72][73] In December 2020, doctors from Lurie Children's pioneered the use of gene replacement therapy to treat a case of a baby with type 1 spinal muscular atrophy, a disease that deteriorates the muscles.

[109][110] As of 2021 Lurie Children's has placed nationally in all 10 ranked pediatric specialties on U.S. News & World Report.