Babbage sought a method by which mathematical tables could be calculated mechanically, removing the high rate of human error. Three different factors seem to have influenced him: a dislike of untidiness; his experience working on logarithmic tables; and existing work on calculating machines carried out by Wilhelm Schickard, Blaise Pascal, and Gottfried Leibniz. He first discussed the principles of a calculating engine in a letter to Sir Humphry Davy in 1822.

Babbage's engines were among the first mechanical computers, although they were not actually completed, largely because of funding problems and personality issues. He directed the building of some steam-powered machines that achieved some success, suggesting that calculations could be mechanized. Although Babbage's machines were mechanical and unwieldy, their basic architecture was very similar to a modern computer. The data and program memory were separated, operation was instruction based, the control unit could make conditional jumps and the machine had a separate I/O unit.

In Babbage’s time numerical tables were calculated by humans called ‘computers,’ meaning "one who computes," much as a conductor is "one who conducts." At Cambridge he saw the high error rate of this human-driven process and started his life’s work of trying to calculate the tables mechanically. He began in 1822 with what he called the difference engine, made to compute values of polynomial functions. Unlike similar efforts of the time, Babbage's difference engine was created to calculate a series of values automatically. By using the method of finite differences, it was possible to avoid the need for multiplication and division.

The first difference engine was composed of around 25,000 parts, weighed fifteen tons (13,600 kg), and stood 8 ft (2.4 m) high. Although he received ample funding for the project, it was never completed. He later designed an improved version, "Difference Engine No. 2", which was not constructed until 1989-1991, using Babbage's plans and 19th–century manufacturing tolerances. It performed its first calculation at the London Science Museum returning results to 31 digits, far more than the average modern pocket calculator.

Babbage designed a printer for the second difference engine which supported line-wrapping, variable column and row width, and programmable output formatting.

Ada Lovelace, an impressive mathematician and one of the few people who fully understood Babbage's ideas, created a program for the Analytical Engine. Had the Analytical Engine ever actually been built, her program would have been able to calculate a sequence of Bernoulli numbers. Based on this work, Lovelace is now widely credited with being the first computer programmer. In 1979, a contemporary programming language was named Ada in her honour. Shortly afterward, in 1981, a satirical article by Tony Karp in the magazine Datamation described the Babbage programming language as the "language of the future".

Babbage also achieved notable results in cryptography. He broke Vigenère's autokey cipher as well as the much weaker cipher that is called Vigenère cipher today. The autokey cipher was generally called "the undecipherable cipher", though owing to popular confusion, many thought that the weaker polyalphabetic cipher was the "undecipherable" one. Babbage's discovery was used to aid English military campaigns, and was not published until several years later; as a result credit for the development was instead given to Friedrich Kasiski, a Prussian infantry officer, who made the same discovery some years after Babbage.

In 1838, Babbage invented the pilot (also called a cow-catcher), the metal frame attached to the front of locomotives that clears the tracks of obstacles. He also constructed a dynamometer car and performed several studies on Isambard Kingdom Brunel's Great Western Railway in about 1838. Babbage's eldest son, Benjamin Herschel Babbage, worked as an engineer for Brunel on the railways before emigrating to Australia in the 1850s.

In On the Economy of Machine and Manufacture, Babbage described what is now called the Babbage principle, which describes certain advantages with division of labor. Babbage noted that highly skilled - and thus generally highly paid - workers spend parts of their job performing tasks that are 'below' their skill level. If the labor process can be divided among several workers, it is possible to assign only high-skill tasks to high-skill and -cost workers and leave other working tasks to less-skilled and paid workers, thereby cutting labor costs. This principle was criticized by Karl Marx who argued that it caused labour segregation and contributed to alienation. The Babbage principle is an inherent assumption in Frederick Winslow Taylor's scientific management.

Babbage once counted all the broken panes of glass of a factory, publishing in 1857 a "Table of the Relative Frequency of the Causes of Breakage of Plate Glass Windows": 14 of 464 were caused by "drunken men, women or boys". His distaste for commoners ("the Mob") included writing "Observations of Street Nuisances" in 1864, as well as tallying up 165 "nuisances" over a period of 80 days; he especially hated street music.