Jet2 plan a four-night trip to the capital of Massachusetts and airline bosses are likely to make the Transatlantic trip an annual event if the launch attracts enough passengers.
Like Chicago, where the waters of the river run green on the big day, Boston is famed for its Irish themed parades and parties to toast St Patrick.
St Patrick's Day will be celebrated on Monday, March 17, and Jet2 will be flying revellers out of Glasgow three days earlier for the airline's inaugural spring break to Boston.
Passengers will touch back down in Glasgow on March 18.
Steve Heapy, chief executive of both Jet2.com and Jet2holidays, said: "Today marks a milestone for Jet2holidays at Glasgow with the expansion of our Transatlantic routes.
"We are very excited with the launch of Boston - it is an amazing place to visit especially for St Patrick's Day and I'm sure it will be a success."
He added: "The addition of this route - our sixth to launch this year - reinforces our commitment to offering our local customers an unrivalled choice of great value breaks to a wide range of exciting European and inter- national destinations direct from their doorstep."
Airport chiefs in Glasgow welcomed the Boston special. Commercial director Francois Bourienne said: "Since arriving in 2011 Jet2.com has been quick to identify destinations for regular scheduled services and, as in this case, one-of flights.
"Previous one-ofs such as the Christmas shopping flights to New York have been very successful and Boston should be no different as it is a fantastic city which really comes alive at St Patrick's Day every year."
The decision to link Scotland's biggest city with Boston comes just three weeks after Jet2 officials took the wraps off plans for a one-of shopping trip to the Christmas markets of Cologne in Germany to compliment their annual festive flight to New York.