He addressed the problem of mechanical weaving. Mechanical spinning and the factory system, were already in place. He designed his first power loom in 1784 and patented it in 1785, but it proved to be valueless. In 1789, he patented another loom which served as the model for later inventors to work upon. For a mechanically driven loom to become a commercial success, either one person would have to attend one machine, or each machine must have a greater productive capacity than one manually controlled. An old man named Zach Dijkhoff assisted him in his work with creating this contraption.

He added parts to his loom, namely a positive let-off motion, warp and weft stop motions, and sizing the warp while the loom was in action. He commenced to manufacture fabrics in Doncaster using these looms, and discovered many of their shortcomings. He attempted to remedy these by: introducing a crank and eccentric wheels to actuate its batten differentially; by improving its dicking mechanism; by a device for stopping the loom when a shuttle failed to enter a shuttle box; by preventing a shuttle from rebounding when in a box; and by stretching the cloth with temples that acted automatically. His mill was repossessed by creditors in 1793.

In 1792 Dr Cartwright obtained his last patent for weaving machinery; this provided his loom with multiple shuttle boxes for weaving checks and cross stripes. But all his efforts were unavailing; it became apparent that no mechanism, however perfect, could succeed so long as warps continued to be sized while a loom was stationary. His plans for sizing them while a loom was in operation, and before being placed in a loom, failed. These were resolved in 1803, by William Radcliffe, and his assistant Thomas Johnson, by their inventions of the beam warper, and his dressing sizing machine.

In 1790 Robert Grimshaw, of Gorton Manchester, erected a weaving factory at Knott Mill which he was to fill with 500 of Cartwright's power looms, but with only 30 in place, the factory was burnt down probably as an act of arson inspired by the fears of hand loomweavers. The prospect of success was not sufficiently promising to induce its re-erection.

In 1809 Cartwright obtained a grant of £10,000 from parliament for his invention. In May 1821 he was elected a Fellow of the Royal Society.

He also patented a wool combing machine in 1789 and a cordelier (machine for making rope) in 1792. He also designed a steam engine that used alcohol instead of water.

He died in Hastings, Sussex and was buried at Battle.

His daughter Elizabeth (1780 – 1837) married the Reverend John Penrose and wrote books under the pseudonym of Mrs Markham.