The new show celebrates the 25th anniversary of the original Super Dimension Fortress Macross TV series (1982–1983), and is chronologically subsequent to Macross 7 (1994–1996). This third TV series introduces Earth's latest main variable fighter, the VF-25 Messiah (メサイア)^[3] and a new ship called the Macross Frontier. The show retains the signature space opera theme consistent with all series set in the Macross universe (which intertwine musical numbers with fast-paced variable fighter combat). New episodes aired weekly on the MBS network Thursdays at 25:55 and on the TBS network Fridays at 25:55 (the 24+ hour clock is a common Japanese TV broadcast notation). Three separate manga adaptations have been running in Shōnen Ace and Comp Ace, since February 2008, April 2008, and July 2008, respectively.

On the Macross timeline, the story is set in 2059, 47 years after the original Super Dimension Fortress Macross, 19 years afterMacross Plus and 14 years after the story of Macross 7. The series features the 25th New Macross-class Colonial Fleet, dubbed theMacross Frontier, en route to the galactic center. This heavily populated interstellar fleet (consisting of numerous civilian vessels and their military escorts) contains a makeup of both human occupants and their Zentradi allies. As such, many of the Macross Frontier's companion vessels appear to merge more metallic Human designs with organic Zentradi aesthetics. Macross Frontier‍‍ '​‍s plot explores a combination of action/political intrigue/space drama more than previous Macross series have done in the past.

As the series begins, during a mission to an unexplored asteroid belt a reconnaissance New U.N. Spacy (N.U.N.S.) VF-171 is destroyed by extremely powerful and fast insectoid biomechanical alien mecha known as the "Vajra" (バジュラ),^[4] which immediately begin their attack on the rest of the fleet. Unable to stop the new enemy threat, the N.U.N.S. Colonial Defense Forces authorizes the deployment of a private military provider organization called S.M.S. (Strategic Military Services) which utilizes the new VF-25 Messiahvariable fighter to combat the alien menace.

Like other installments of the Macross universe, the story mainly revolves around a trio of characters, including Alto Saotome, a young pilot who joins the S.M.S just after the invasion begins, Sheryl Nome, a famous singer known as the "Galactic Fairy" and Ranka Lee, a teenager aspiring to be a singer herself, that form a love triangle.