The M110, along with the M107, formed a pair of nearly identical self-propelled guns introduced in the early 1960s, essentially the heavy counterparts to the medium-caliber M108 and M109 which also entered service at the same time. They were designed to replace the M55 which was the largest calber SPG used by the US at the time. The M110 shared the same chassis as the M107, these featuring an all-welded aluminum hull with the driver seated at the front left and the turbocharged diesel engine to their right. A large spade was fitted in the rear of the hull and there were additional mechanisms fitted to the road wheels to improve stability when firing. Armament consisted of a 203-mm M115 howitzer (a redesignated 8-inch M1 gun of World War II vintage) on an open mount, which could fire to a maximum range of 16.8 km at a rate of one round per minute. This made it decidedly inferior in both range and rate of fire to the M107, although it was compensated by the greater destructive power of the 203-mm shell which included the ability to fire tactical nuclear rounds. Later variants would extend the range to 22.9 km. However, the lack of storage space mean that the M110 could only carry two rounds, necessitating the use of a M548 tracked cargo carrier at all times. The M110 was not fitted with defensive armament or NBC protection, and also lacked amphibious capability but it was air-transportable in a C-5. The M110 was first used in combat by the US Army during the Vietnam War. Unlike the M107, however, it remained in service until the mid-1990s and saw action in the Gulf War as well. It was supplied to numerous NATO countries, notably Germany, Greece, Italy, Turkey, and the UK (which used it in the Gulf War as well), as well as other US allies including Israel, Japan, Jordan, Pakistan, and South Korea many of which converted their M107s into M110s. It remains in service with many of them to this day.

Development took place concurrently with the M110, with the prototype designation being T235 before entering production as the M110. Incremental improvements resulted in the M110E1 and later the definitive M110A1. This featured a longer barrel which could fire more advanced ammunition which increased its range. This variant also served as a replacement for the M107, most of which were converted to the new standard. The addition of a double-baffle muzzle brake resulted in the M110A2, to which most existing units were converted to.