Factual error: Before receiving the North American P-51D Mustangs, the Red Tail squadron was using the Curtiss P-40E Warhawk. The movie shows the Warhawks being able to keep up with the German Bf 109 G-6s quite easily, fighting on even terms. In reality, the Bf 109 G-6 could easily outperform the Warhawk, being able to easily outrun and out-turn the Warhawk. Still, the Bf 109s are no match for the Warhawks.
Factual error: The German fighters depicted in the film are Messerchmitt Bf 109 G-6s, and every single one of them is using the Rüstsatz VI gun pod, that is, 2 extra 20mm Mg 151 cannons. The Luftwaffe only equipped their Bf 109s with the gun pods when they were going to intercept bombers. In this movie, even on the fighter vs fighter missions, they have these gun pods, which is inaccurate, because the gun pods dramatically reduced the turning performance of the Bf 109s.
Factual error: The German fighters in the movie are Bf 109 G-6s, which are armed with 2 13.2mm Mg 131 machine guns and one 20mm Mg 151 cannon, but they are shown equipped with the Rüstsatz VI gun pods in the wings, which are 2 extra Mg 151s. That is a very heavy armament, capable of shooting down even a Boeing B-17 Flying Fortress quickly. Still, the Mustangs and Warhawks used by the Red Tails are shown taking lots of hits and still flying with relative ease. The P-51D Mustang and the P-40E Warhawk were indeed quite rugged and damage resistant, but 3 20mm cannons and 2 13.2mm machine guns are more than enough to shoot them down with even a 1 second burst.
Factual error: When the German fighter ace (called "Pretty Boy" by the Tuskegee Airmen) attacks the B-17s, he says "Brecht ein und zieht die Kämpfer ab!" What he wanted to say is "Break through and distract the fighters" but his choice of words is more like "Break in (as break into) and pull (draw) the fighters off!"
Continuity mistake: When Lightning drives off to meet with Sophia for the first time, he gets into a Jeep with the number 20860779, but when he arrives at Sophia's house, the Jeep has the number 20207765.
Factual error: The Me-262 fighters the 332nd engaged at the end of the movie were armed with 30mm cannon. A hit with one of those shells was enough to bring a B-17 down. An explosion of one in a P-51 cockpit would have shredded Lightning instead of leaving a neat bullet wound in his chest.