Design work on a new family of pistols commenced in September 1989 focused primarily on the United States commercial and law enforcement markets. USP prototypes participated in rigorous testing alongside H&K's entry in the Offensive Handgun Weapon System (OHWS) program requested by the U.S. Special Operations Command (USSOCOM) and which would later result in the Mk 23 Mod 0. The USP prototypes were then refined in 1992, based on input from the OHWS trials, and the design was finalized in December of the same year. The USP was formally introduced in January 1993 with the USP40 model (the base version) chambered for the increasingly popular .40 S&W cartridge, followed soon by the USP9 (using the 9×19mm Parabellum cartridge), and in May 1995—the USP45 (caliber .45 ACP). In contrast to the ambitious and innovative P7, P9S, and VP70Z designs, the USP uses a more conventional Browning-style cam-locked action, similar to that used in the Hi-Power, but with a polymer frame.
The HK45 represents an evolutionary advancement of the Heckler & Koch USP, and shares the same operating principles of that weapon. It is available in the same ten variants as the USP. The HK45 is a full size model pistol, but significant effort went towards making it more ergonomic than the HK USP full-size chambered in .45 ACP by incorporating features found on the Heckler & Koch P2000. These include an extended ambidextrous slide release, a textured ergonomic grip with finger grooves, and interchangeable backstraps to fit differently sized hands. The newer grip and backstraps allow the pistol to sit lower into the web of the hand, contributing to greater control of the weapon and recoil management. In order to accommodate the smaller, more ergonomic grip, the HK45 has a magazine capacity of 10 rounds versus 12 rounds for the USP45. The HK45 also added grip serrations on the front end of the slide, a Picatinny rail in front of the trigger guard for mounting accessories, and an O-ring polygonal barrel similar to the USP Expert and Match models and the Mark 23 for more consistent lock-up of the slide and barrel during cycling and increased accuracy.
At least one HK45C Tactical was used in Operation Neptune Spear.
The HK45 is also the first weapon to be manufactured at Heckler & Koch's new facility in Newington, New Hampshire.
Heckler & Koch also manufactures the HK45 Compact (HK45C), which can use an 8-round and a 10-round magazine. The HK45C features the same improvements as the full-size HK45, but has a more conventional straight grip similar to Heckler & Koch's P2000. This design still allows the user to customize the grip size via interchangeable backstraps.
An HK45 Tactical (HK45T) and HK45 Compact Tactical (HK45CT) are also available; these variants include an extended threaded barrel for suppressors, and tritium front and rear sights. Extended threaded barrels compatible with the HK45 and HK45C are also available for purchase from Heckler & Koch USA.