Currently, there are more people in Middletown of Italian, or mixed-Italian ancestry, than of any other ethnic group. Though many have come from Northern Italy, there have been a substantial number arriving from Melilli, Sicily, who have played a crucial role in developing the character of Middletown. Middletown's population in 1900 was 17,464, and by 1910 immigration had increased it to almost 21,000.

The African American population in Middletown began declining in the 1860s with the influx of European immigrants. Local employers were more likely to hire white Europeans, and African Americans found it increasingly difficult to secure industrial employment. In 1830, there were 208 people of African descent. By 1910 only 73 African Americans resided in the city, and in 1920, only 53 remained.

During the first part of this century, Middletown helped fight World War I and subsequently enjoyed an expanding abundance. It oversubscribed most of the Liberty Loans, and its factories, such as Russell Manufacturing, had shifted to produce war material. Fifteen hundred Middletown residents served in World War I, of whom 37 did not return home.

After the war, Middletown joined the nation in drinking from the cup of prosperity during the "Roaring Twenties." The seven automobiles that the city boasted in 1903 were multiplied many times by 1929, including several from Middletown's own Eisenhuth Horseless Vehicle Company. New houses went up in many parts of the city, and the brickyards in the Newfield area flourished.

This abundance continued until the Great Depression began in 1929. Though certainly many residents were hit hard, the Depression did not strike Middletown as devastatingly as it hit other cities. Concerted efforts by local manufacturers, with federal and state aid, helped Middletown survive difficult times.

These difficulties were compounded by a debilitating flood in 1927, only to be followed by an even more damaging flood in 1936, both of which claimed numerous lives and caused millions of dollars in property damage. Then, having barely recovered, Middletown was again struck by nature on September 21, 1938, by the "Great New England Hurricane," with winds of over 170 miles per hour. Though no one was killed in Middletown, many homes were damaged irreparably.

From 1936 to 1938 the Arrigoni Bridge connecting Middletown and Portland was constructed, named after Senator Charles J. Arrigoni of Durham. During these years, arduous work on the bridge took place virtually 24 hours a day.

World War II had an enormous effect on Middletown's community. Approximately 3,700 women and men served overseas, while life at home was affected substantially. Women had comprised only one-quarter of the work force outside the home before the war, a proportion which dramatically rose as they filled spaces left in factories by absent male soldiers. Many African American families from the South traveled to Middletown to seek employment in factories, thereby boosting their numbers, which had dwindled in the early part of the century.

Middletown maintained a stable economic base after World War II. Route 9 was constructed in 1950 for a population made mobile by advancements in automobile design and affordability. Though the Goodyear Rubber Plant and other factories closed their doors during the 1960s, Pratt and Whitney Aircraft, a section of United Technologies, opened a factory of their own in 1966, and has remained a central economic force in the area.

Charles Ghent came to Middletown from the South in the early 1940s, and for thirty years was one of the foremost spokespersons for civil rights as President of the Middletown Branch of the NAACP (National Association for the Advancement of Colored People) founded in 1943. During the 1960s, he rallied for the integration of Middletown schools, as neighborhoods had become increasingly segregated as a result of discrimination in housing.

The Civil Rights Movement experienced significant achievements in Middletown, including an NAACP organized march in early 1963 down Main Street calling for federal troops to be sent to Birmingham, Alabama; a demonstration in March of 1965, with over 300 protesters marching down Main Street for racial justice; and a takeover by African American students of Fisk Hall at Wesleyan University in February of 1969, demanding equity in education.

From 1970 to 1990, the Hispanic population in Middletown more than doubled, with a marked increase in the number of people from Puerto Rico. During the early 1980s, more shifts in demographics contributed to the diversity of Middletown, when hundreds of people from Southeast Asia arrived, particularly from Thailand and Cambodia.