In 1944, after enduring racism throughout their recruitment and training in the Tuskegee training program, the 332d Fighter Group of young African American USAAF fighter pilots are finally sent into combat in Italy, although flying worn-out Curtiss P-40 Warhawk aircraft. Chafing at their ground attack missions against trains and enemy ground transport, the Tuskegee Airmen recognize that they may never fight the Luftwaffe in fighter-to-fighter combat. The tight-knit group of Capt. Martin "Easy" Julian (Nate Parker), Lt. Joe "Lightning" Little (David Oyelowo), Ray "Ray Gun" or "Junior" Gannon (Tristan Wilds), and Samuel "Joker" George (Elijah Kelley) under the guidance of Major Emanuel Stance (Cuba Gooding, Jr.) and Col. A.J. Bullard (Terrence Howard), face a white military bureaucracy still resistant to accepting colored fliers as equals.Strife develops between roommates and best friends, Easy and Lightning, each of whom are battling their own inner demons; Lightning is a hotheaded and reckless pilot who takes too many risks, while Easy is an alcoholic prone to self doubt. After returning to base from a mission, Lightning spies a pretty Italian girl named Sofia (Daniela Ruah), becomes instantly infatuated with her, and starts a relationship.Meanwhile, Stance is able to secure a chance to "light up the board" when the Tuskegee Airmen are chosen to support the Allied landings at Anzio, Italy known as Operation Shingle. There, they battle Messerschmitt Bf 109 fighters led by a German ace pilot they nickname, "Pretty Boy" (Lars van Riesen), scoring their first aerial victories over the enemy, as well as destroying a German airfield. However, Ray Gun is injured during the battle and suffers impaired vision in one of his eyes. Ray Gun begs Easy to keep him on the flight roster who ultimately relents and allows him to keep flying.Bullard is then approached by the USAAF Bomber Command, who are impressed with the Tuskegee Airmen's performance and ask him to use his fighters as Boeing B-17 Flying Fortress bomber escorts due to unacceptably high casualties among bomber crews. Bullard accepts on the condition that his unit be supplied with the new North American P-51 Mustang. The tails of the aircraft are painted bright red and become the unofficial name of the outfit. Bullard noted that the flaw of previous escort fighters is that they would recklessly pursue German fighters at the cost of protecting the bombers, so he orders his pilots to stay with the bombers at all costs. Their first escort mission is a success, with the 332nd downing multiple Luftwaffe aircraft without the loss of a single bomber. However, Ray Gun is shot down and captured while Deke crash lands and nearly dies.As a result of his injuries, Deke is discharged, and Ray Gun is assumed to be dead. Easy realizes it was his fault Ray Gun was allowed to fly, blames himself and spirals deeper into alcoholism. Lightning, worried about his friend, makes a deal with Easy; he will follow orders and fly less recklessly as long as Easy remains sober.Meanwhile, attitudes against the Tuskegee Airmen begin to change as they earn the bomber crews' respect, even being allowed into the "whites only" officer's club. Ray Gun is sent to a POW camp, where he is recruited by a group of POWs who are planning to escape. The escape attempt is successful, but some of the POWs are spotted by a guard so Ray Gun draws the Germans' attention while the other POWs escape. One of the POWs manages to reach the 332nd's base and informs them about Ray Gun's sacrifice, assuming him to be dead. Later, Lightning finally proposes to Sofia and though she originally hesitates, she later accepts as long as he stays in Italy, which he agrees to do.The Tuskegee Airmen are then tasked with escorting the first American bombers to attack Berlin. However, despite their P-51s having more than enough fuel for the trip, the 332nd is only asked to escort the bombers on the first leg of their journey due to propaganda reasons. But the fighter squadron meant to relieve the 332nd never arrives, and Easy makes the decision to stay with bombers all the way. They are then attacked by Pretty Boy, now leading a flight of the revolutionary new Messerschmitt Me 262 jet fighters. Despite being outclassed by their superior speed and 30 mm cannon, the Tuskegee Airmen are able to shoot a few down. Pretty Boy manages to get on Easy's tail and is about to shoot him down, but at the last moment, Lightning attacks and kills Pretty Boy in a head-on attack. Although victorious, he is mortally wounded, and Lightning eventually crashes and dies. Easy is then forced to inform Sofia about Lightning's death and consequently overcomes his alcoholism for good. At Lightning's funeral, Ray Gun miraculously returns, having survived his escape from German captivity.Ultimately, the Tuskegee Airmen are awarded the Presidential Unit Citation in honor of their achievements.