The progress of these projects was slow but after Germany had declared war on the United States four days after the Pearl Harbor attack by Imperial Japan, the Reichsluftfahrtministerium (RLM) started the more serious Amerikabomber programme in the spring of 1942 for a very long range bomber, with the result that a larger, six-engine aircraft with a greater bomb load was called for.

Proposals were put forward for the Junkers Ju 390, the Focke-Wulf Ta 400, a redesign of the Heinkel He 277 design (itself only receiving its RLM airframe number by February 1943 to give Heinkel an entry in the Amerikabomber program later in 1943), and a design study for an extended-wingspan six-engine Messerschmitt Me 264B.

The Me 264 was not abandoned as the Kriegsmarine (German navy) separately demanded a long-range maritime patrol and attack aircraft to replace the converted Fw 200 Condor in this role.

The fuselage was round in cross-section and had a cabin in a glazed nose, comprising a "stepless cockpit" with no separate windscreen section for the pilots, which was common for most later German bomber designs.

The planned armament consisted of guns in remotely operated turrets and in positions on the sides of the fuselage.

To provide comfort on the proposed long-range missions, the Me 264 featured bunk beds and a small galley complete with hot plates.

In addition, the first prototype was not fitted with weapons or armour, the weight of which would have caused worse performance.

The second prototype, Me 264 V2, was completed with armour around the engines, crew and gun positions, but defensive weapons and other vital operational equipment were never fitted.

The Luftwaffe indicated a preference for the unbuilt Ta 400 and the Heinkel He 277 as Amerikabomber candidates in May 1943, based on their performance estimates.

[3][5] On 18 July 1944, the first prototype, which had entered service with Transportstaffel 5, was damaged during an Allied bombing raid and was not repaired.