The Ju 52 was similar to the company's previous Junkers W33, although larger. In 1930, Ernst Zindel and his team designed the Ju 52 at the Junkers works at Dessau. The aircraft's unusual corrugated duralumin metal skin, pioneered by Junkers during World War I, strengthened the whole structure.

The Ju 52 had a low cantilever wing, the midsection of which was built into the fuselage, forming its underside.  It was formed around four pairs of circular cross section duralumin spars with a corrugated surface that provided torsional stiffening. A narrow control surface, with its outer section functioning as the aileron, and the inner section functioning as a flap, ran along the whole trailing edge of each wing panel, well separated from it. The inner flap section lowered the stalling speed and the arrangement became known as the Doppelflügel, or "double wing".

The outer sections of this operated differentially as ailerons, projecting slightly beyond the wing tips with control horns. The strutted horizontal stabilizer carried horn-balanced elevators which again projected and showed a significant gap between them and the stabilizer, which was adjustable in-flight. All stabilizer surfaces were corrugated.

The fuselage was of rectangular section with a domed decking, all covered with corrugated light alloy. There was a port side passenger door just aft of the wings, with windows stretching forward to the pilots' cabin. The main undercarriage was fixed and divided; some aircraft had wheel fairings, others not. There was a fixed tail skid, or later tail wheel. Some aircraft were fitted with floats or skis instead of the main wheels.

In its original configuration, designated the Ju 52/1m, the Ju 52 was a single-engined aircraft, powered by either a BMW or Junkers liquid-cooled engine. However, the single-engine model was underpowered, and after seven prototypes had been completed, all subsequent Ju 52s were built with three radial engines as the Ju 52/3m (drei motoren - "three engines"). Originally powered by three Pratt & Whitney Hornet radial engines, later production models mainly received 574 kW (770 hp) BMW 132 engines, a licence-built refinement of the Pratt & Whitney design. Export models were also built with 447 kW (600 hp) Pratt & Whitney Wasp R-1340 and 578 kW (775 hp) Bristol Pegasus VI engines. The two wing-mounted radial engines of the Ju 52/3m had full-chord cowlings and were noticeably toed-out, from being mounted at an almost perpendicular angle to the wing's tapered leading edge. The central engine had a half-chord cowling like a Townend ring as the fuselage behind it was increasing in diameter, though some later aircraft had deeper cowlings. Production Ju 52/3m aircraft flown by Luft Hansa before World War II, as well as Luftwaffe-flown Ju 52s flown during the war, usually used an air start system to turn over their trio of radial engines, using a common compressed air supply that also operated the main wheels' brakes.

In 1934, Junkers received orders to produce a bomber version of the Ju 52/3m to serve as interim equipment for the bomber units of the still secret Luftwaffe until it could be replaced by the purpose designed Dornier Do 11.  Two bomb-bays were fitted, capable of holding up to 1,500 kg (3,300 ) of bombs, while defensive armament consisted of two 7.92mm MG 15 machine guns, one in an open dorsal position, and one in a retractable "dustbin" ventral position, which could be manually winched down from the fuselage to protect the aircraft from attacks from below. The bomber could be easily converted to serve in the transport role.^[7] The Dornier Do 11 was a failure, however, and the Junkers ended up being acquired in much larger numbers than at first expected, with the type being the Luftwaffe's main bomber until more modern aircraft such as the Heinkel He 111, Junkers Ju 86 and Dornier Do 17 entered into service.

The Ju 52 first saw military service in the Spanish Civil War against the Spanish Republic. It was one of the first aircraft delivered to the fraction of the army in revolt in July 1936 as both a bomber and transport. In the former role, it participated in the bombing of Guernica. No more of the bomber variant were built after this war, though it was again used as a bomber during the bombing of Warsaw during the Invasion of Poland of September 1939. The Luftwaffe then relied on the Ju 52 for transport roles during World War II, including paratroop drops.

Hitler used a Deutsche Luft Hansa Ju 52 for campaigning the 1932 German election, preferring flying to transport via train. After he became German Chancellor in 1933, Hans Baur became his personal pilot, and Hitler was provided with a personal Ju 52. Named Immelmann II after the World War I ace Max Immelmann, it carried the designation D-2600.  As his power and importance grew, Hitler's personal air force grew to nearly 50 aircraft, based at Berlin Tempelhof Airport and made up of mainly Ju 52s, which also flew other members of his cabinet and war staff. In September 1939 at Baur's suggestion, his personal Ju 52 Immelman II was replaced by the four-engine Focke-Wulf Fw 200 Condor, although Immelman II remained his back-up aircraft for the rest of World War II.

Various Junkers Ju 52s continued in military and civilian use following World War II. In 1956, the Portuguese Air Force, who was already using the Ju 52s as a transport plane, employed the type as a paratroop drop aircraft for its newly organized elite parachute forces, later known as the Batalhão de Caçadores Páraquedistas. The paratroopers used the Ju 52 in several combat operations in Angola and other Portuguese African colonies before gradually phasing it out of service in the 1960s.

The Swiss Air Force also operated the Ju 52 from 1939 to 1982 when three aircraft remained in operation, probably the last and longest service in any air force.  They are still in flying condition and together with a CASA 352 can be booked for sightseeing tours with Ju-Air.  During the 1950s the Ju 52 was also used by the French Air Force during the Indo-China War as a bomber. The usage of these Junkers was quite limited.

The Spanish Air Force operated the Ju 52, nicknamed Pava, until well into the 1970s. Escuadrón 721 flying the Spanish-built versions, was employed in training parachutists from Alcantarilla Air Base near Murcia.

Some military Ju 52s were converted to civilian use. For example, British European Airways operated eleven ex-Luftwaffe Ju 52/3mg8e machines, taken over by the RAF, between 1946 and retirement in 1947 on intra-U.K. routes before Dakotas took over.  French airlines such as Societe de Transports Aeriens (STA) and Air France flew Toucans in the late 1940s and early 1950s.

A Ju 52 and a Douglas DC-3 were the last aircraft to take off from Tempelhof Airport before all operations ceased there on October 30, 2008.