Henry Charles Lea was born in Philadelphia, Pennsylvania, on September 19, 1825, the son of Isaac Lea and Frances Anne Carey. He had two siblings, Matthew Carey (1823-1897) and Frances (1834-1894). Educated privately, he worked for his father's publishing house, Lea & Blanchard (also known as Blanchard and Lea, and as Henry C. Lea), from 1843-1881. Lea earned an academic reputation for his publications on subjects such as the history of Spain, and received honorary degrees from multiple universities. On May 27, 1850, he married Anna Caroline Jaudon, the daughter of William Latta Jaudon and Susan G. Lea. They had four children: Francis Henry (1851-1902), Charles Matthew, Anna (b. 1855), and Arthur Henry. Henry Charles Lea died in 1909. Anna Jaudon Lea's sister Elizabeth married Henry Lea's brother, Matthew Carey Lea, in 1852, after the death of her first husband, William Woodhouse Bakewell of New Orleans, Louisiana.