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The PZL.49 was a development of the advanced, "state-of-the-art"[1] medium bomber PZL.37 Los, designed by Jerzy Dabrowski, Stanislaw Kot and Piotr Kubicki.[2] About 50% of its design elements were taken from PZL.37 Los bomber to simplify the design process. The main target for the design team was to increase performance, especially flight speed, by means of installing more powerful engines and improving aerodynamics. Its standard 2,200 kg (4,900 lb) bomb load could be increased to 3,000 kg (6,600 lb) by decreasing its fuel load. Its standard 2,200 km (1,200 nmi) range could be increased to 3,000 km (1,900 nmi) with additional fuel tanks.

Detailed project was ready in mid-1938 and a report by General Józef Zajac from 28 November 1938 stated that all drawings were complete. Design process was slow due to the simultaneous involvement of PZL construction bureau in development of the PZL.50 Jastrzab fighter. During the summer of 1939, a mock-up of the PZL.49 was approved by the Air Force and project could be continued. Due to the engagement of Jerzy Dabrowski in PZL.62 development, Piotr Kubicki became the leader of the PZL.49 design team.

In late 1938 or early 1939 production of parts for two prototypes begun in Wytwórnia Platowców nr 1 of PZL factory (PZL WP-2). In early 1939 a full-scale mock-up of fuselage with part of the left wing was built for testing placement of cockpit and fuselage equipment.

Serial production was planned to take place in the PZL WP-2 factory in Mielec as well as construction bureau HQ. A development schedule from August 1939 set the first flight of PZL.49/I in the summer of 1940, with the first serial built aircraft being delivered to combat units in late 1941 or early 1942. However, due to the German invasion on 1 September 1939, all plans were canceled. All documentation of the PZL.49 project was moved to Jerzy Dabrowski's apartment in Warsaw early September 1939 and in late September, during siege of Warsaw, was burned in a nearby bakery to avoid German capture. Very little of the documentation has been recovered since the war.

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