Masters of the Air is the third and final companion miniseries following Band of Brothers (2001) and The Pacific (2010), but it is the only one of the three not to air on HBO.

The project was first reported in 2012 as being considered by Tom Hanks and Steven Spielberg, and HBO confirmed in January 2013 that it was developing the series based on Donald L. Miller's book, adapted by John Orloff.

In October 2019, Apple made a deal with Spielberg's and Hanks's production companies to move the series to Apple TV+ exclusively, with HBO later confirming it had dropped the project; it became the first Apple TV+ series produced under Apple's in-house Apple Studios.

Principal photography began in February 2021 at Dalton Barracks, the former WWII airfield RAF Abingdon in Oxfordshire, England, with additional filming in Hemel Hempstead.

Filming was paused briefly in July 2021 due to positive COVID-19 tests among the crew, part of several delays caused by strict pandemic-related government measures.

A temporary WWII-style barracks set was built at Newland Park in Chalfont St Peter, for which retrospective 12-month planning permission had to be applied for.

The series used on-set virtual production technology by Lux Machina for the cockpit scenes, and a total of 3,447 visual effects shots were created for the miniseries, with DNEG handling 1,600–2,000 shots including most aerial sequences.

Despite generally positive reviews (85% on Rotten Tomatoes), the series faced criticism for historical inaccuracies, a lack of strategic narrative context, and CGI aerial scenes that some critics described as making the B-17 bombers look 'cartoonish'.

A companion documentary titled The Bloody Hundredth, narrated by Tom Hanks, was released on Apple TV+ on March 15, 2024, detailing the real story of the 100th Bomb Group that inspired the series.