Preparations for the possibility of war introduced the 1st Pursuit Group to a new weapon. In July 1941, the 27th Pursuit Squadron received the P-38 "Lightning," the first in the Army Air Force's inventory. The Group would have just six months to acquaint itself with their new addition when on December 7, 1941, the Japanese launched a surprise attack against air and naval targets stationed in Hawaii, propelling the United States into war.

The United States wanted to cover any vulnerabilities on the West coast to any Japanese attack and tasked the 1st and its assigned squadrons from Selfridge to March Field, California. During their short time at March Field the Group was slowly being plucked of its personnel, losing over half of their assigned officers and enlisted men. Short of men and morale, the Group prepared to deploy for Europe on 25 April 1942. Before they left, however, an alumnus of theirs, Eddie Rickenbacker, made one of his two visits to the Group during World War II. The retired captain listened to the Group’s concerns and reported them to General Henry "Hap" Arnold. Rickenbacker also worked with Arnold to reinstate the hat-in-the ring emblem, absent since Rickenbacker himself claimed the right to it when he retired, back to the 94th.

In 1942, military strategists decided that Hitler's Germany posed a greater threat than Japan, and placed first priority with the war in Europe. As a result, the newly designated 1st Fighter Group deployed to England in what was to be called Operation Bolero. During the summer of 1942, the 1st flew once again, training and occasional fighter sweeps over the skies of France. The Group received the call to move again, this time to North Africa. By 13 November 1942, the Group completed the move to Algeria, where they provided aerial support against German occupied territories.

On 29 November 1942, the 94th Fighter Squadron flew the Group's first combat sorties of World War II, strafing a German airfield and recording several aerial victories. However, as the year came to a close, the Group's morale sagged. Few replacement parts and virtually no replacement aircraft were available; and although the Group recorded some kills, the tally against the enemy was even at best. For nearly a year, the Group moved throughout Algeria and Tunisia, flying bomber escort and providing air coverage for the ground campaign. Allied forces pushed the Germans back, and the North African campaign ended with the capture of Tunis on 7 May 1943.

Six months of continuous, heavy fighting in North Africa was followed by a short break, flying reconnaissance and escort missions around the Mediterranean. The respite ended on 15 August, as air attacks increased against southern Italy. On 25 August, after much practice, the 1st launched 65 aircraft, and joined with 85 more, for a historic attack against the Italian Foggia airfield complex. In addition to strafing ground targets, pilots of the 1st damaged or destroyed 88 enemy aircraft, with a loss of two P-38s. For this mission, the group received its first distinguished unit citation (DUC). Five days later, the group participated in a mission earning their second DUC. The 1st launched a 44-ship formation, escorting B-26 bombers to the railroad marshalling yards at Aversa, Italy. Approximately 75-100 aircraft suddenly attacked the formation. Outnumbered two to one, the Group persevered through a 40-minute air battle, and although losses were even on both sides, the bombing mission continued, unabated. As a result the escorted bombers struck their target and returned to base without a loss. The Group hopped from base to base in Italy, before settling at Salsola Airfield, on 8 January 1944. Living and supply conditions improved for the airmen, who received new P-38Js in the spring. On 16 April 1944, the group flew its 1,000th combat mission.

The 1st Fighter Group received its third DUC for action on 18 May 1944. That day's target was the oil fields at Ploesti, Romania. The fighters were scheduled to escort 700 bombers; however, bad weather caused many bombers to abort the mission. Nonetheless, the fighters continued through the heavy weather in case any bombers had continued to the target. When the P-38s reached the target, 140 American bombers were under attack by 80 enemy fighters. The Group's 48 P-38s attacked the German fighters, driving them off. The pilots shot down and damaged nearly 20 enemy aircraft, with a loss of one P-38, whose pilot parachuted to safety.

The remainder of the war proved less eventful for the Group, as the air war in Italy came to a close. On 11 August 1944, the 1st deployed sixty aircraft to Corsica, assisting in the allied invasion of Southern France known as Operation Dragoon.

The Group's last major operation of the war came in January 1945. Under Operation Argonaut, the Group escorted British and American delegations to the Yalta Conference. A total of 61 aircraft deployed in missions escorting the ships and aircraft carrying President Franklin Roosevelt, Prime Minister Winston Churchill, and their aides to and from the Crimea. On 15 April 1945, the 27th Fighter Squadron, who earlier scored the Group's first kill of the war, recorded the Group's last kill of the war.

During nearly three years of combat flying, the 1st Fighter Group flew over 21,000 sorties on over 1,400 combat missions.

As was custom, the United States demobilized after the war. However, with its tradition and heritage, the 1st Fighter Group remained at the forefront. Returning to March Field, California, the group once again made history when it was assigned America's first operational jet fighter, the P-80 "Shooting Star". Shortly afterward the arsenal would evolve into the P-86 "Sabre". After its independence in September 1947 the Air Force would re-designate the Ps to Fs the following June.