The first airfields in the Keweenaw Peninsula were, as common at the time, near the shoreline; several are known to have existed on both sides of the Portage Canal, with airmail and ad hoc passenger service to Chicago's Meigs Field. These fields could not accommodate increasingly larger aircraft in the post-WWII era, and their locations made them unsuitable for expansion. Houghton County Memorial Airport was commissioned at its current location in 1948, with air service on Wisconsin Central Airlines commencing a few months later via milk run service to Chicago and Detroit via many intermediate stops.

For the next sixty years, Wisconsin Central's corporate successors - sequentially, North Central Airlines, Republic Airlines, Northwest Airlink operated by Simmons Airlines, Mesaba Airlines, and Pinnacle Airlines, and Delta Connection - maintained regular passenger service, to varying combinations of Chicago, Detroit, and Minneapolis. Flights to Detroit usually included a stop at Marquette County Airport until 1999, and Sawyer International Airport from 1999-2003, when direct service to Detroit was cancelled in favor of exclusive service to Minneapolis.

Following the great recession in 2008-2009 and corresponding reduction in passenger traffic, Mesaba Airlines filed for subsidized service under the Essential Air Service program. Despite strong community support for Mesaba's service, the FAA instead selected Skywest Airlines, operating as United Express, making two daily flights to Chicago. On March 11, 2022, SkyWest announced its intention to withdraw from the airport (and 30 others), which would leave the airport with no scheduled passenger service. The airport rejected the airline's plans to reduce flight frequencies to the airport, however, and SkyWest continues to operate twice-daily flights, albeit with a much higher EAS subsidy.