In 1927, Whitall, independently of the city commission, set up an airport on his land in North Grafton, 500 feet (150 m) above sea level.

The location of the present airport, Tatnuck Hill, on the borders of Worcester, Leicester, and Paxton, was high on the commission's list.

It still sits, now mostly overgrown in the shadow of Worcester Regional which in 1969 was served by Northeast Airlines with McDonnell Douglas DC-9-30 jet and Fairchild Hiller FH-227 turboprop flights nonstop to New York LaGuardia Airport as well as to nearby Boston and Manchester, NH.

[7][8] Northeast Airlines was then acquired by and merged into Delta Air Lines which in 1973 was continuing to serve Worcester with McDonnell Douglas DC-9-30 jet service nonstop to New York LaGuardia Airport and Manchester, NH as well as direct, no change of plane DC-9 jet service to Atlanta, Boston and New Orleans.

[13] In 1981, two commuter airlines were serving Worcester: Bar Harbor Airlines operating Convair 600 and Beechcraft 99 turboprop aircraft with nonstop service from New York LaGuardia, Hartford and Manchester, and Precision Airlines operating shuttle service into the airport with thirteen nonstop flights operated every weekday from Boston Logan International Airport (BOS) flown with small Piper Navajo twin engine piston aircraft.

In the mid-1980s and early 1990s, major carriers, such as Piedmont, Northwest Airlines, Continental, and USAir all flew mainline jets into Worcester.

Allegiant announced on August 22, 2006, that they would cut ties with the airport, citing high fuel costs and passenger loads in the 80% range as the reason for departure.

The announcement of flights ending took people by surprise as service was popular and well-regarded by the flying public throughout Allegiant's entire tenure at the airport.

However, Direct Air was required to return the aircraft in June 2009 to suffice Virgin's rapidly expanding domestic routes.

The airline had further plans to launch flights to San Juan, Puerto Rico, and Nassau, Bahamas, but in March 2012 Direct Air suspended all operations and later filed for Chapter 7 bankruptcy on April 12, 2012.

A revamp of the defunct airline Air Florida had planned to fly out of Worcester at the beginning of 2015 as a scheduled charter operation.

On February 28, 2017, JetBlue announced it would expand its service at the airport, adding a daily non-stop flight to New York City.

JetBlue did not provide a start date, but airline officials said the new flights would not begin until after the landing system was operational.

[24] On April 9, 2018, American Airlines announced it would begin daily non-stop service from Worcester to Philadelphia on October 4, 2018.

[26] Despite the efforts to add an additional frequency, Piedmont announced in February, only four months into service, a reduction to only one daily flight, starting in June 2019 due to low demand.

There was initially speculation that the Saturday flight would possibly return in May, but the future of service remained uncertain, with Delta experiencing 50-60 percent loads to Detroit.

On January 13, 2021, within the documentation for their Northeast Agreement alliance with American Airlines, it was initially confirmed that JetBlue's station at the airport was closed permanently, along with Oakland and Long Beach, once again leaving Worcester with no scheduled commercial service.

Worcester Regional Airport was used for shooting of the films Captain Phillips, Knight and Day, The Judge and The Sea of Trees.

On April 28, 2016, Massport approved funding for the installation of a Category IIIb instrument landing system at ORH.

The geographic location of the airport, on top of the tallest hill in the city reaching approximately 1,000 feet above sea level, leaves Worcester on average with 40 more days of fog a year than nearby Boston.

[42] Completion of the ILS allowed JetBlue to add a flight from Worcester to New York-JFK, operated with an Embraer 190 aircraft capable of autoland.

However, American's flight to their Philadelphia hub was operated by an Embraer 145 aircraft which was not able to use the newly installed Category III system which led to many weather cancellations and diversions during their second brief tenure.

On the morning of October 25, 2015, Dr. Gary Weller crashed his light Mooney M20M plane into nearby woods while attempting to take off in cold weather on Runway 11.

[54][55] On February 2, 2021, a Piper PA-46 from Martha's Vineyard crashed in nearby Leicester while attempting an emergency landing at ORH.