Born in 2155, Joker's upbringing and career have been colored by his health. Joker has a moderate to severe case of Vrolik syndrome, which causes extreme brittleness in the bones; he was born with severe fractures to his legs and even with modern medicine he finds walking nearly impossible, relying on crutches and leg braces.
Joker spent his early life on Arcturus Station because of his mother's job there as a civilian contractor, and grew up around ships. When he was old enough to enlist, he joined the Alliance Navy. He got his nickname from his flight school instructor, due to the fact that he rarely smiled — he was working too hard. By the end of his training, however, Joker surpassed the other students and even his instructors. "They all got their asses kicked by the sickly kid with the creaky little legs. One guess who was smiling at graduation." When the Normandy was commissioned, Joker was chosen as her pilot.
Because he has difficulty walking, Joker rarely leaves the Normandy's bridge. Despite the fact that he is continually making wisecracks, Joker takes his job very seriously and claims he's the best pilot in the entire Systems Alliance. An example of his exceptional skill was a risky maneuver where he was able to successfully drop the Mako with only twenty meters of open ground (even as other crewmen declared such a drop impossible with anything less than a hundred meters). He has complete faith in Commander Shepard's leadership and the two of them share a good camaraderie.
Joker is essentially the "voice" of the Normandy while Shepard is ashore, and often acts as Shepard's eyes and ears, particularly on Feros and Virmire. Though lighthearted, Joker is not completely insensitive; after Virmire, if Shepard talks to him, Joker talks about having to choose between Ashley Williams and Kaidan Alenko, and needs some time on his own to grieve. If Shepard decides not to bother telling the Council about Sovereign after Virmire, Joker rather prophetically snorts that Sovereign will have to be sitting on the Citadel's roof before the Council will listen to them, but Joker promises Shepard he's in it to the end. He wants to be there when Shepard makes Saren Arterius pay.
While Shepard's team is on Ilos (thanks to Joker's expertise in dropping the Mako) and investigates the Conduit, Joker takes the Normandy to the Andura Sector and rallies the Fifth Fleet to defend the Citadel against Sovereign. When Shepard returns to the Citadel, the Commander manages to get in touch with Joker, who's sitting beside a mass relay waiting for Shepard to unlock the relay network. Joker then coordinates strategy with Shepard, asking if they should defend the Destiny Ascension to save the Council, or go straight in for the kill. Either way, the Normandy leads the Alliance forces in the battle against Sovereign — Joker's skills mean that despite Sovereign's heavy firepower, the Normandy barely gets a scratch.
Joker is on board the Normandy as it is attacked by an unknown enemy. Shepard tries to convince Joker to abandon the ship, but Joker insists he can save it, despite other crew evacuating and the ship sustaining catastrophic damage. Shepard tells him that going down with the ship won't change anything and hauls him to the nearby escape pod. Unfortunately, just as the Commander places Joker in the pod, a blast separates them. Joker escapes to safety, while Shepard suffocates in the void.
After the destruction of the Normandy and Shepard presumed to be killed in action, Joker was reassigned, along with the rest of the surviving Normandy crew members. However, Cerberus' plan to rebuild and bring Shepard back to life led Joker to join the pro-human organization, mainly to be the pilot of the new Normandy SR-2 as a member of Lazarus Cell. He also received an upgrade for his legs that allows him to walk on his own, albeit with some difficulty. Joker is quite fond of the new Normandy setup, relishing the comfort of his pilot bay. However, he resents the presence of the shipboard AI, EDI. The two engage in a war of sorts, with pranks ranging from Joker greasing the cameras to EDI spinning his seat about against his will. EDI claims she is just testing Joker under stress, as she notices that he works better when pushed. Despite Joker's initial hostility towards EDI, he later gains a begrudging respect for her.
This trust is put to the test when the Normandy is engaged by the Collectors and Joker loses all control of the ship due to a virus hidden in the IFF, at the same time as Shepard and the team are away on a mission. EDI urges Joker to release her control lock and give control of the ship so she can initiate countermeasures protocol. Although Joker feels hesitant at the suggestion, he has no choice but to make his way down to the A.I. Core room, avoiding Collectors and Scions along the way while watching fellow crew members get captured. When Joker successfully links EDI to the Normandy's core control systems, he crawls down the shafts again into the engine room and manually restarts the power core, granting EDI full control of the ship. EDI jumps the Normandy to safety, clearing the Collectors and Scions on-board the ship in the process, leaving Joker the only survivor in this incident. Throughout the confrontation with the Collectors on the Normandy, Joker becomes a playable character and if the player-controlled Joker is spotted by enemies, he will be taken by a Scion or killed by a Praetorian, resulting in a critical mission failure.
After the Collector attack and EDI's full capability unlocked, Joker begins to display a newfound fondness for EDI as she helps ease up his task load and performs the duties of the abducted crew. Joker subconsciously begins referring to EDI as "she" for the first time. When Shepard asks if a relationship is growing between the two, Joker laughs off the notion and EDI describes the relationship as a "platonic symbiosis" rather than a "hormonally-induced courtship behavior".
As the suicidal assault on the Collector base commences, Joker successfully pilots the Normandy SR-2 through the Omega 4 relay and the debris field that follows despite the Normandy taking damage, including several hull breaches. As Shepard runs towards the Normandy after defeating the final boss, Joker appears at the door of the Normandy with an M-8 Avenger and gives Shepard covering fire, enabling surviving squadmates to pull the Commander inside, given at least two squadmates survived the suicide mission. If at least two squadmates didn't survive the mission, Shepard dies despite Joker's valiant effort. At the end of the assault, Joker manages to fly the Normandy away from the Collector base before it is either destroyed or purged based on Shepard's decision.
In either ending for the game, Joker acquires the schematics of a Reaper, presumably Harbinger, gained from EDI hacking the Collector base's computers. If Shepard fails to escape the Collector base, Joker is seen briefly mourning over the Commander's coffin, and Joker will speak to the Illusive Man in the mission debriefing instead.
Since Shepard surrendered to Alliance custody, Joker still remained at his position onboard the Normandy, which became renovated by the Alliance. He also told EDI to pose as a VI, so the Alliance wouldn't dismantle her for being an AI.
Joker has an... interesting relationship with EDI.