Hornet arrived at Naval Air Station Alameda, California on 20 March 1942. With her own planes on the hangar deck, by midafternoon on 1 April she loaded 16 B-25s on the flight deck. Under the command of Lieutenant ColonelJames H. Doolittle, 70 officers and 64 enlisted men reported aboard. In company of her escort, Hornet departed Alameda on 2 April  under sealed orders. That afternoon, Captain Marc Mitscher informed his men of their mission: a bombing raid on Japan.
Eleven days later, Hornet joined the aircraft carrier Enterprise offMidway, and Task Force 16 (TF 16)  turned toward Japan. WithEnterprise providing combat air cover, Hornet was to steam deep into enemy waters. Originally, the task force intended to proceed to within 400 nmi (460 mi; 740 km) of the Japanese coast; however, on the morning of 18 April, a Japanese patrol boat, No. 23 Nitto Maru, sighted the American task force. Nashville sank the patrol boat.Amid concerns that the Japanese had been made aware of their presence, Doolittle and his raiders were forced to launch prematurely from 600 nmi (690 mi; 1,100 km) out instead of the planned 450 nmi (520 mi; 830 km). Because of this decision, none of the 16 planes made it to their designated landing strip in China. After the war, it was found that Tokyo received the Nitto Maru's message in a garbled form and that the Japanese ship was sunk before it could get a clear message through to the Japanese mainland.
As Hornet swung about and prepared to launch the bombers, which had been readied for take-off the previous day, a gale of more than 40 kn (46 mph; 74 km/h) churned the sea with 30 ft (9.1 m) crests; heavy swells, which caused the ship to pitch violently, shipped sea and spray over the bow, wet the flight deck and drenched the deck crews. The lead plane, commanded by Colonel Doolittle, had only 467 ft (142 m) of flight deck, while the last B-25 hung its twin rudders far out over the fantail. Doolittle, timing himself against the rise and fall of the ship's bow, lumbered down the flight deck, circled Hornetafter take-off, and set course for Japan. By 09:20, all 16 were airborne, heading for the first American air strike against the Japanese home islands.
Hornet brought her own planes on deck as TF 16 steamed at full speed for Pearl Harbor. Intercepted broadcasts, both in Japanese and English, confirmed at 14:46 the success of the raids. Exactly one week to the hour after launching the B-25s, Hornet sailed into Pearl Harbor.Hornet's mission was kept an official secret for a year; until then President Roosevelt referred to the base the bombers started from only as "Shangri-La". Several years later, the USN would give this name to an aircraft carrier.
On 28 May, Hornet and Task Force 16 steamed out of Pearl Harbor heading for Point "Luck", an arbitrary spot in the ocean roughly 325 miles northeast of Midway, where they would be in a flank position to ambush Japan's mobile strike force of four frontline aircraft carriers the Kido Butai. Japanese carrier-based planes were reported headed for Midway in the early morning of 4 June 1942. Hornet, Yorktown, and Enterprise launched aircraft,  just as the Japanese carriers struck their planes below to prepare for a second attack on Midway.Hornetdive bombers followed an incorrect heading and did not find the enemy fleet. Several bombers and all of the escorting fighters were forced to ditch when they ran out of fuel attempting to return to the ship.  Fifteen torpedo bombers of Torpedo Squadron 8 (VT-8) found their enemy and pressed home their attacks. They were met by overwhelming fighter opposition about 8 nmi (9.2 mi; 15 km) out, and with no escorts to protect them, they were shot down one by one. EnsignGeorge H. Gay, USNR, was the only survivor of 30 men. 
Further attacks by Enterprise and Yorktown torpedo planes proved equally disastrous, but succeeded in dispersing both the carriers and their fighter cover. Japanese fighters were finishing off the last of the torpedo planes over Hiryū when dive bombers of Enterprise and Yorktown attacked and sank the three remaining Japanese carriers. Hiryu was hit late in the afternoon of 4 June by a strike from Enterprise and sank early the next morning. Hornet aircraft, launching late due to the necessity of recovering Yorktown scout planes and faulty communications, attacked a battleship and other escorts, but failed to score hits. Yorktown was lost to combined aerial and submarine attack. 
Hornet's planes attacked the fleeing Japanese fleet on 6 June 1942, and assisted in sinking the cruiser Mikuma, damaging a destroyer, and left the cruiser Mogami aflame and heavily damaged. Her attack on Mogami ended one of the decisive battles of history.  Midway was saved as an important base for operations into the western Pacific. Of greatest importance was the crippling of Japan's carrier strength, a severe blow from which they never fully recovered. The four large carriers took with them to the bottom some 250 aircraft and a high percentage of Japan's most highly trained and battle-experienced carrier pilots. The victory at Midway is widely seen as a turning point in the battle for the Pacific