Isaac Howell was born in 1810 in Hancock County, Georgia. Isaac Howell’s father was Joseph Howell (born about 1771 in North Carolina) and Nancy, last name unknown, (born about 1786 in North Carolina). Joseph Howell (b: ca. 1771) is on the 1850 Hancock County, Georgia, census, listed in the household of family # 400, Nancy Howell, age 64, born in North Carolina. Joseph is listed as being age 79 in 1850, born in North Carolina. The Nancy on the 1850 census is likely a daughter of Joseph Howell, age 79 in 1850. Joseph Howell was the son of Matthew Howell (b: ca. 1747 in NC) and Temperance Cavenah.

Isaac Howell married Mary Angeline Davis (born 30 January 1817 in Hancock County, Georgia) on 13 October 1835.

The children of Isaac Howell and Mary Angeline Davis were:
1. Leonidas W. Howell(born: 1837 in Georgia)
2. Henry Howell (born 1839 in Georgia)
3. Thaddeus (born 1841 in Alabama)

Isaac Howell, his wife, and family moved to Lafayette, Chambers County, Alabama in 1840. Isaac Howell farmed in Alabama. Mary Angeline Davis Howell died in Lafayette, Alabama, leaving Isaac with their three children. Being apprised of Mrs. Howell's (Mary A. Davis Howell) illness, her mother, Mrs. Samuel Davis, and her sister, Mrs. Thomas Stocks, went in their carriage to Lafayette, Alabama. Mrs. Isaac Howell died soon after they reached there. Isaac Howell consented for Mrs. Stocks to bring two of the boys back to Georgia, and she reared and educated them at Mercer University when it was located at Penfield, Greene County, Georgia. Isaac’s son, Henry Howell, was mentally retarded, so he remained with Isaac in Lafayette. However, Thaddeus and Leon’s education was not complete when the War Between the States began in 1860. Both boys, "Thad" and "Lee" enlisted in the Confederate army, and both were killed at Gettysburg.

After the death of Mary Angeline Davis Howell Isaac married Elizabeth Grey (born about 1820 in South Carolina), on 30 March 1844 in Chambers County, Alabama.

Issac Howell and Elizabeth Grey had the following children:
1. Mary Ann Howell (born: 9 Sep 1845 in Alabama died: 10 Jan 1912 in Smith County, Texas)
2. Joseph D. Howell (born: 1848 in Alabama)
3. Nancy Howell (born: 1850 in Alabama)
4. Carrie Ada Howell (born: 1853 in Alabama)
5. William Howell (born: 1855 in Alabama)
6. Annie Howell (born: 1859 in Alabama)
7. Martha C. Howell (born: 1861 in Alabama)

Sometime prior to 1872, Isaac Howell’s second wife, Elizabeth Grey, died. Isaac Howell moved to Cherokee County, Texas, in 1872 or 1873. With him were his daughter, Mary Ann Howell Towles, and her two daughters, Sarah Towles and Elizabeth “Lizzie” Lee Towles; his daughters, and two sons. Mary Ann Howell Towles husband, Albert Towles, was already in Texas having come to Anderson County, Texas, after the Civil War.

Isaac Howell died on 15 February 1889 in Cherokee County, Texas.