When Colt decided that it wanted a piece of the Derringer market, it used a tactic we are used to seeing today: it found an existing manufacturer and just bought them outright. This was the National Firearms Company, which was manufacturing a Derringer designed by Daniel Moore in 1861. Moore made the guns himself until 1865 when he sold the rights to National, and they made them until being purchased by Colt in 1870. This design then became the Colt 1st Model (and 2nd Model) Derringer. It used a knife blade type extractor, and was offer in all-metal construction (the 1st model) or with wood or ivory grip panels (the 2nd model). Both of these Moore designed types were made until about 1890, with about 15,000 total being made.

In about 1875, Colt engineer F. Alexander Thuer (who previously designed Colt's cartridge conversion for percussion revolvers) designed his own Derringer. This used a barrel that open to the side, and a spring extractor. It was more efficient to produce than the Moore design, and it became the Colt 3rd Model Derringer. It was produced until 1912, with about 48,000 total made. Production of a 4th Model actually began in 1959, with periodic production runs. These last guns were in .22 rimfire.

The first three Colt Derringers are all chambered for the common .41 rimfire cartridge, with occasional very limited production in .41 centerfire. The standard barrel length was just 2.5 inches, although many variations exist in small numbers.