With war with the Pirate Clans looming, an uprising begins among the Neosapiens, an artificial humanoid race coexisting with Terrans. In the back-story, the Neosapiens were used primarily as slaves during the colonization of Mars and Venus and therefore have been engineered to be physically stronger and better adapted to hostile environments than humans. Their mistreatment by Terrans led to the First Neosapien Revolt fifty years before the series' begin, which was mercilessly crushed but had brought some positive changes into their lives. Still not content with his fate, the Neosapien Governor of Mars, Phaeton, sets a new insurrection, codenamed "Operation [Neosapien] Destiny", in motion as soon as the Exofleet leaves to chase after the Pirate Clans. The absence of the Exofleet is also a part of Phaeton's plan as it enables the Neosapiens capture the Homeworlds without much effort.
The two seasons that the series was on the air follow the progress of the Neosapien War, as seen through the eyes of Able Squad, an elite E-frame unit, comprised of J.T. Marsh, Nara Burns, Maggie Weston, Kaz Takagi, Alec DeLeon, Rita Torres, Wolf Bronsky, and Marsala (see Cast). Their exploits unfold against the backdrop of the on-going war, as the squad participates in events often crucial to turning its tide. The show features a realistic outlook on war: many characters die in combat, military operations are carefully planned and reconnoitered in advance, and psychological effects of warfare are explored. For example, separate episodes detail Exofleet's reconnaissance of Venus prior to its recapture, the actual liberation, and the repulse of the first Neosapien reconquest attempt. Moreover, even after Venus is retaken by Terrans, several episodes deal with the remaining Venusian resistance and Neosapien forces who hid across Venus, refusing to surrender and awaiting reinforcements.
The second season draws to a close with the defeat of the Neosapiens and the liberation of Earth, but it ends with a cliffhanger suggesting that a third season would describe a war against a new alien race, and that the Terrans and the Neosapiens would be forced to ally with each other. However, the series was cancelled soon after the end of the second season so a third season was never made (see Production).
Exosquad features an ensemble cast that portrays eight members of the Able Squad.
While the main focus of the show is on the Able Squad, individual episodes and story arcs are frequently dedicated to other characters as well. For example, the C5 Jumptroop Squadron, several Homeworlds Resistance cells, prominent Pirates, and high-ranking Neosapien officers are all given much screen time.
Exosquad had a very serious approach to the plot with several intertwined narrative threads and a number of characters displaying a full spectrum of human emotions, relationships and experiences, such as friendship, love, hatred, personal tragedies, treachery and taking responsibility for others. Michael Edens, the story writer and editor in the second season, credited the show's realism for much of its success. Prejudice and racism are recurring themes in the series, as both Terrans and Neosapiens are shown to harbor hatred and a sense of superiority towards each other. Interplanetary politics and space war typical for military science fiction were presented with an assumption of the fictional future history of the Solar System up to that point. The Able Squad's duties became more spread out as the second season unfolded, and there were separate story arcs on Mars, Venus, Earth, and in space. Espionage and intrigue were often featured instead of straightforward battles.
Will Meugniot, the executive producer of the series, once compared anime series Mobile Suit Gundam and Exosquad to the Pacific and the European Theaters of World War II, respectively. Michael Edens recalled in an interview that the plot was supposed to remind of the Second World War, too, for example with the Neosapien reconquest attempt of Venus, capture of the Moon and battle for Chicago paralleling the battles of the Bulge, Okinawa, and Berlin, respectively. The viewers also pointed out parallels between the villainous Neosapien leader, Phaeton, and Adolf Hitler of the Third Reich.
The series owes its title to the Exo-Frames (commonly referred as E-frames): multi-purpose mecha-like powered exoskeletons mostly utilized as armored combat vehicles or reinforced body armour by the characters.
Exosquad was among the first animated series by Universal Animation Studios (then known as Universal Cartoon Studios) and was created under heavy influence of anime imported from Japan. As a result, its complex story line covered a large number of topics from war through romance to genetic engineering and was able to appeal to a broad audience. Although the first season ran for only thirteen episodes in 1993, the rising popularity of the show allowed Universal to make the second one thrice as long. In its second season, Exosquad was put into the "Universal Action Hour" together with Monster Force.
As the second season progressed, some characters, according to Michael Edens, "took on a life of [their] own": for example, Nara Burns killing Phaeton and the Neosapien Thrax becoming a major recurring character after his initial appearance were not pre-planned. Another character, Alec DeLeon, was supposed to perish in the destruction of Mars but the Universal executives strongly opposed it, so he was killed several episodes later, on the Moon, only to be promptly resurrected in a Neo Mega body.
The show was purportedly cancelled after 52 episodes because at that time, many independent production companies were being taken over by larger networks, who wanted to produce their own content. Exosquad was eventually moved to poor time slots, such as 4 a.m., until the ratings were no longer sufficient to sustain it. The final episode detailed the post-war political and social climate prevalent in the Exosquad universe, and closed with J.T. Marsh engaging a group of alien space vessels, whose exact nature was to be explained in the third season or a feature movie. Michael Edens later remarked that the staff originally planned the aliens to be insectoid and that the Pirates' dark matter, Dr. Ketzer's experiments, and the unactivated clone of Phaeton would have played a great role in fighting them. The idea of a movie based on Exosquad was being promoted by executive producer Jeff Segal and it was also planned to expand the fictional universe with a spin-off series, then codenamed Exo-Pirates. Both initiatives were scrapped with the cancellation of the third season.
The first season of Exosquad has been released on seven VHS cassettes shortly after its original run and in 2007, it was made available on Hulu video on demand service. No official DVDs were produced by Universal, although bootleg copies have been circulating through online stores. Between 1993 and 1996, Playmates Toys produced a line of action figures and model kits of E-frames and spaceships featured in the television series. The descriptions of the toys are a major source of Exosquad universe lore. The toys were often compared to the popular Robotech franchise, and Playmates acquired the license to Robotech to produce both toy lines under the same label, spawning rumors of a possible crossover. This possibility was considered by the authors but later abandoned. Additionally, a Sega Genesis console video game under the same name was developed by Appaloosa Interactive, and a comic book, an interactive movie book and a board game based on the series were released.