Lewis L. Winfrey was born into slavery around 1838 in Albemarle County, Virginia, and worked as a farmer. His owner brought him to Ohio around the early 1850s, set him free, and helped him acquire a homestead. By 1860, he was living with his brother John and their parents in Fayette County, Ohio.

He enlisted in the Union army in Fayette County on June 7, 1863, for a period of three years. Later that day, he mustered in as a private in Company E of the 127th Ohio Colored Infantry Regiment, which later became the 5th USCT Infantry Regiment. His enlistment record describes him as 5 feet, 8 inches tall, with black hair, black eyes, and a brown complexion. His regiment performed garrison duty throughout Virginia and North Carolina and took part in the Siege of Petersburg. During the Petersburg campaign, a shell struck his left hip and left hand while he constructed breastworks near Fort Stedman, Virginia, on July 22, 1864. He convalesced in the hospital for months and received a furlough in the spring of 1865. He rejoined his regiment in May and performed garrison and guard duty in Carolina City, North Carolina. He mustered out on September 20, 1865.

Winfrey returned to Fayette County after mustering out. He married a woman named Patience, who died on March 22, 1868. He married Sarah Ward on January 6, 1870, in Clinton County, and they had six children together: Lewis H., born October 14, 1873; Parthena, born around 1876; Nancy, born around 1879; Clarence, born March 27, 1881; Daisy Belle, born August 9, 1888; and Eulalie, born July 2, 1891. In December 1871, Winfrey and Sarah moved to Paulding County, Ohio, where Winfrey worked as a farmer and minister. He applied for a pension in 1876 and eventually began receiving $8 per month. His health, however, continued to decline, and by 1886, severe rheumatism left him partially paralyzed and unable to walk without assistance. He died of severe progressive locomotor ataxia in Paulding County on February 24, 1895, and was buried in Abbott Cemetery.