What is now DE 72 originally existed as a county road by 1920. By 1931, the road was proposed as a state highway between present-day DE 9 and US 13 while what would become DE 72 north of Milford Crossroads was completed as a state highway. The road from present-day DE 9 to US 13 became a state highway a year later. On July 1, 1935, the remaining sections of the present-day route were transferred from the county to the state. The portion of the road between US 13 and US 40 was improved by the state in 1937, providing a better route to
Baltimore and
Washington, D.C. for residents in the Delaware City,
Port Penn, and
Odessa areas. DE 72 was designated by 1942 to run from DE 2 (Main Street) in Newark north to DE 7, following Chapel Street and Paper Mill Road. In 1939, suggestions were made to replace the bridge over the White Clay Creek along Paper Mill Road in Newark. Plans were completed for this bridge by 1942 but construction was postponed due to
World War II. The concrete bridge carrying Paper Mill Road over the White Clay Creek was completed in 1947, with final work on the project finished in August 1949. By 1954, Sunset Lake Road was improved from a dirt road to a low-type bituminous road. The roadway between US 40 and Newark was paved by 1966. DE 72 was extended to its present southern terminus at DE 9 the next year, following Chapel Street, Sunset Lake Road, and Wrangle Hill Road. In 1980, the Chapel Street grade crossing of the Northeast Corridor rail line in Newark was removed, and DE 72 was realigned farther to the east to follow Library Avenue across the railroad tracks before continuing north on DE 2 and Possum Park Road to Paper Mill Road in Milford Crossroads. DE 2 was realigned to follow DE 72 around the eastern part of Newark on Library Avenue by 1990. In 2013, the DE 2 concurrency between DE 4 and DE 273 was removed due to the truncation of DE 2 to the DE 273 intersection. On April 29, 2016, Governor
Jack Markell, DelDOT secretary Jennifer Cohan, and local officials attended a groundbreaking ceremony for a $7 million project that rebuilt the interchange with DE 1 into a diverging diamond interchange, the first such interchange in Delaware. The diverging diamond interchange configuration was put into place on November 19, 2016. ==Major intersections==