He was born in 1807, the son of William Smith, who came from Massachusetts to teach school in frontier Tennessee.

Dr. Smith's mother was Elizabeth Cozby, daughter of the famous East Tennessee physician and Indian fighter, Dr. James Cozby.  His father, William Smith went from Knoxville to Washington in Rhea County in 1812. He founded Smith's Crossroads (Dayton) after purchasing 60 acres there in 1820.

Dr. Milo Smith studied medicine at the Philadelphia Medical School in Pennsylvania.  He had “a great deal of information on almost every subject pertaining to matters Biblical and historical, but especially physic”.

Milo Smith had come down river from Rhea County to the new Ross's Landing settlement where his sister, Eliza, had moved with her husband, John P. Long. From the commissioners who had laid out and were selling off Chattanooga lots, he purchased lot 38 on Poplar Street for $220 in 1840.

He sold this lot and built on lot 42 nearby. At the time of the Indian removal, both Dr. Smith and his father worked with the government.  William Smith relocated to Rawlingsville, Ala., in this capacity. Dr. Smith made several trips between Ross's Landing and the Indian Territory with the Cherokees.

Milo Smith married Caroline Lipscomb, who was from Grainger County, Tenn., and was the daughter of Spotswood and Elizabeth Smith Pendleton Lipscomb. Their son, William Spotswood Smith, graduated from medical school at Nashville. He entered Confederate service and was on the medical staff of Dr. Samuel H. Stout.

Dr. Milo Smith's daughter, Elizabeth Nisbet Smith, was the first white child born in Chattanooga after it was named - her birth being Christmas Day 1838. She married Andrew Mitchell Macmurphy of Augusta, Ga., in 1859. Macmurphy's sister was the wife of another Chattanooga mayor, Charles Grenville.

Dr. Smith was one of the founders of the Presbyterian Church at Chattanooga.  He was also the leading medical practice, but he seemed almost unconcerned about whether or not he was paid.  It was said by old citizens, that Mayor Dr. Milo Smith waited upon the entire city of Chattanooga without charge and that, in a sense established the first free clinic in the city.  It is told that he never sent a bill to anyone.  His clients paid when they pleased, if at all.

He seems to have been, without exception, the most popular citizen in Chattanooga’s early life and Dr. Smith was so well liked by the community that several babies were named in his honor.

Dr. Milo Smith served his first term as Mayor in 1842 and was re-elected in 1843, making him the first mayor to serve two terms.

The Milo Smiths remained in Chattanooga throughout much of the war between the States at their brick home on Cameron Hill on the east side of Poplar Street between Fifth and Sixth streets.  Dr. Smith served as mayor again in 1862 and 1863, until his office was abrogated by Military Occupation.

He treated many wounded soldiers from both armies in the war-torn city.  Caroline Smith took care of a baby who had lost its mother when only six weeks old and whose father was one of the artillerymen under the duty of firing shells into Chattanooga. Dr. Smith early in 1864 “felt it necessary to leave Chattanooga.” His home on Poplar Street was sold to John G. Glass. The Milo Smiths returned after the war and Dr. Smith had a drug store with John Bailey Nicklin at Fifth and Market.