The river begins as two individual streams. The West Branch of the DuPage River, 35. 0 miles (56. 3 km) long, starts at Campanelli Park in Schaumburg within Cook County and continues southward through the entire county of DuPage, including the towns of Bartlett, Wheaton, Warrenville, Winfield and Naperville (including through its riverwalk).

DuPage County was formed on February 9, 1839 out of Cook County. The county took its name from the DuPage River, which was, in turn, named after a French fur trapper, DuPage. The first written history to address the name, the 1882 History of DuPage County, Illinois, by Rufus Blanchard, relates:

The Du Page River had, from time immemorial, been a stream well known. It took its name from a French trader who settled on this stream below the fork previous to 1800. Hon. H. W. Blodgett, of Waukegan, informs the writer that J. B.

Like many local bodies of water, both branches of the DuPage River seriously overflowed after the "Flood of 1996", when approximately 17 inches (430 mm) of rain fell on the area within a 24-hour period, on July 18–19 of that year.