The Uzi uses an open-bolt, blowback-operated design, quite similar to the Jaroslav Holeček-designed Czech ZK 476 (prototype only) and the production Sa 23, Sa 24, Sa 25, and Sa 26 series of submachine guns. The open bolt design exposes the breech end of the barrel, and improves cooling during periods of continuous fire. However, it means that since the bolt is held to the rear when cocked, the receiver is more susceptible to contamination from sand and dirt. It uses a telescoping bolt design, in which the bolt wraps around the breech end of the barrel. This allows the barrel to be moved far back into the receiver and the magazine to be housed in the pistol grip, allowing for a heavier, slower-firing bolt in a shorter, better-balanced weapon.

The weapon is constructed primarily from stamped sheet metal, making it less expensive per unit to manufacture than an equivalent design machined from forgings. With relatively few moving parts, the Uzi is easy to strip for maintenance or repair. The magazine is housed within the pistol grip, allowing for intuitive and easy reloading in dark or difficult conditions, under the principle of "hand finds hand". The pistol grip is fitted with a grip safety, making it difficult to fire accidentally. However, the protruding vertical magazine makes the gun awkward to fire when prone. The Uzi features a bayonet lug.