Still and his family were among the founders of Baker University in Baldwin City in 1858, the first four-year university in the state of Kansas. Still was involved in selecting the location for the site of Baker University's first building. Along with his brother, Still donated 640 acres of land for the university campus. While maintaining his medical practice, where he treated patients afflicted with small-pox and cholera, Still spent five years building the facilities.

Still was active in the abolition movement and a friend and ally of the infamous anti-slavery Leaders John Brown and James H. Lane. He became deeply embroiled in the fight over whether Kansas would be admitted to the Union as a slave state or a free state. The Kansas–Nebraska Act of 1854 provided that the settlers in those two territories would decide the question for themselves. Civil war raged in Kansas as both sides tried to gain control of the territorial government. In October 1857, Still was elected to represent Douglas and Johnson counties in the Kansas territorial legislature. Still and his brothers took up arms in the cause and participated in the Bleeding Kansas battles (between the pro and anti-slavery citizens). By August 1858, a free-state constitution had been passed; Kansas was admitted to the Union as a free state on January 29, 1861.

After the Civil War and following the death of his wife, three of his children, and an adopted child from spinal meningitis in 1864, Still concluded that the orthodox medical practices of his day were frequently ineffective and sometimes harmful. He devoted the next thirty years of his life to studying the human body and finding alternative ways to treat disease. During this period, he completed a short course in Medicine at the new College of Physicians and Surgeons in Kansas City, Missouri, in 1870.

Still adopted the ideas of spiritualism sometime around 1867, and it "held a prominent and lasting place in his thinking."

Still was fascinated by machines, and whenever faced with a mechanical Problem, his answer was always to devise a better approach. In the 1870s, he patented an improved butter churn. He made improvements to a mowing machine designed to harvest wheat and hay, but before a patent could be submitted, his idea was stolen by a visiting sales representative from the Wood Mowing Machine Co. In 1910, he patented a smokeless furnace burner but had "some difficulty producing a full-sized working model. Heartbroken after his wife, Mary Elvira's, death in May 1910, he did not have the will to pursue the matter further, and the invention was never successfully marketed."

Still founded the first school of osteopathy based on this new approach to Medicine - the school was called the American School of Osteopathy (now A.T. Still University) in Kirksville, Missouri in 1892.

Still published four books during his life. His first book, published in 1897, was entitled Autobiography of Andrew Taylor Still with a History of the Discovery and Development of the Science of Osteopathy. A revised edition of the book was re-published in 1908 after a fire damaged the original printing plates. In 1899, Still published his second book, Philosophy of Osteopathy.

In 1902, Still published his third book, The Philosophy and Mechanical Principles of Osteopathy, although some dispute remains over the date. Still published his fourth and final book in 1910, entitled Osteopathy Research and Practice.

In a 1907 interview by the Topeka Daily Capital newspaper, A.T. Still's son, Charles Still, D.O., described his father's philosophy that the body would operate smoothly into old age, if properly maintained and that every living organism possessed the ability to produce all the necessary chemicals and materials to cure itself of ailments.

In December, 2013 Still was announced as an inductee to the Hall of Famous Missourians. His bronze bust will be one of forty-four on permanent display in the Missouri State Capitol in Jefferson City. For the first time in the hall's history, the public was allowed to vote on new inductees. Still received over 38 percent of the votes, far outdistancing all others in consideration.

Dr. Still sought to reform existing 19th-century medical practices. Still investigated alternative treatments, such as hydropathy, diet, bonesetting, and magnetic healing. Still found appeal in the relatively tame side effects of those modalities and imagined that someday "rational medical therapy" would consist of manipulation of the musculoskeletal system, surgery and very sparing use of drugs, including anesthetics, antiseptics and antidotes. He invented the name osteopathy by blending two Greek roots osteon- for bone and -pathos for suffering in order to communicate his theory that disease and physiologic dysfunction were etiologically grounded in a disordered musculoskeletal system. Thus, by diagnosing and treating the musculoskeletal system, he believed that Physicians could treat a variety of diseases and spare patients the negative side-effects of drugs.