Cleveland Hopkins is of particular importance to the history of commercial air travel due to a number of first-in-the-world innovations that would eventually become the global standard. Founded on July 1, 1925, it was one of the first municipality-owned facilities of its kind in the United States. It was the site of the first air traffic control tower (1929), the first ground-to-air radio control system (1939), and the first airfield lighting system (1930), and it was the first U.S. airport to be directly connected to a local or regional rail transit system (1968).

It was also the first airport to employ a two-level terminal design separating arrivals from departures. The airport was named after its founder, former city manager William R. Hopkins, on his 82nd birthday in 1951.

First closure of United hub, establishment of Continental hub

United Airlines established its easternmost domestic hub in Cleveland after World War II, which it maintained until the mid-1980s, when it closed its Cleveland hub and moved capacity to a new hub at Washington–Dulles. Following the closure of the United hub, Continental Airlines (which at the time was a separate carrier and lacked a Midwest hub) responded by adding capacity to Cleveland, as did USAir, which was the dominant carrier at the airport from 1987 until the early 1990s. While USAir soon reduced its schedule from Cleveland, Continental substantially increased its hub capacity, becoming the airport's largest tenant and eventually accounting for upwards of 60 percent of passenger traffic. Continental and the airport both made substantial operational and capital investments in the airport's infrastructure. In 1992, the airport completed a $50 million renovation of Concourse C, which housed all of Continental's flights. The renovation included the installation of a continuous skylight, a Continental President's Club lounge, and a new Baggage Claim area. In 1999, the airport completed an $80 million expansion that included the construction of the new Concourse D (now closed), which was built to accommodate Continental Express and Continental Connection flights.

In June 1999, Continental Airlines launched flights to London's Gatwick Airport aboard a Boeing 757-200. This was Cleveland's first scheduled transatlantic service, since the 1992 discontinuation of JAT's DC-10 service to Ljubljana and Belgrade, Serbia. The carrier suspended the link after the September 11 attacks and resumed it in April 2002. The following year, Continental made the route seasonal.

Continental began flying into London's Heathrow Airport instead of Gatwick in May 2009; Heathrow offered more connecting flights. The airline discontinued the service four months later, citing the recession and an inability to obtain affordable seasonal slots at Heathrow. The company was also about to join the Star Alliance, to which United Airlines belonged. Consequently, London-bound passengers would be able to transit through United's Chicago hub instead of Cleveland. The cancellation of the route left the city without a direct link to Europe until 2018.

United—Continental merger, second closure of United hub

On May 2, 2010, Continental and United Airlines announced that they would merge operations, completing the integration by October 1, 2010. The merger resulted in the United name being kept and the Continental name disappearing, prompting concerns that a post-merger United would reduce or close its hub in Cleveland and instead route passengers through the new United's Chicago-O'Hare and Washington-Dulles hubs. On November 10, 2010, United/Continental CEO Jeff Smisek stated in a speech in Cleveland that "Cleveland needs to earn its hub status every day" and added that overall profitability would be the determining factor in whether the new United kept or closed the Cleveland hub.

At its peak, United served 68 destinations from Cleveland. United continued to reduce its capacity in Cleveland following the merger, which already had been substantially reduced in the wake of the 2008 financial crisis. On February 1, 2014, United announced that the airline would shut down its Cleveland hub, stating as justification that the airline's hub at Cleveland "hasn't been profitable for over a decade." By June 5, 2014, United had effectively terminated its hub operation at the airport, reducing its daily departures by more than 60%. United also closed Concourse D and consolidated all of its remaining operations in Concourse C, although it is required to continue to pay the airport $1,112,482 a month in rent for the facility until 2027.

Post-hub history

The airport initially experienced a sharp decline in passenger counts following the closure of United's hub in 2014. Several other airlines, however, increased their service to Cleveland in subsequent years. Frontier Airlines significantly increased its service to the airport and declared Cleveland a focus city. New routes connected Cleveland with destinations as far as Luis Muñoz Marín International Airport in San Juan, Puerto Rico.