In 1920 he makes his first guitar out of a cigar box and meets Blind Lemon Jefferson in 1922 who passes on some guitar tips.
Along with his cousin, Texas Alexander, Lightnin' plays the Rainbow Theater in Houston, Texas in 1927.
During the 1930's, Lightnin' leads the life of a hobo, often accompanied by Alexander. He also spends some time in jail during this decade.
As the new decade begins, Lightnin' can be found settled in Houston's black ghetto.
In November 1946 Lightnin' makes his recording debut, on the Aladdin record label, partnered by Wilson Smith, Nicknamed 'Thunder'. The following year with Thunder and Lightnin's first single, 'Katie May' / ' That Mean Old Twister', a jukebox hit, the duo make further recordings for Aladdin. Lightnin' contravenes his contractual agreement with Aladdin to record for the Gold Star label.
Having recorded many superb blues records for Aladdin and Gold Star in the 1940's, Lightnin' records the political song 'Sad News from Korea' in 1951.
Amidst a series of early 1950's recordings for a veriety of labels Lightnin' makes another political statement with 'The Was Is Over' to make the end of the Koren War in 1953.
In 1957 Rock'n'Roll sidelines Lightnin' and he stops recording for a couple of years.
Blues historian Sam Charters tracks Lightnin' to Houston and records the bluesman for his debut album Lightnin' Hopkins in 1959.
Lightnin' begins a lasting partnership with producer Chris Strachwitz of Arhoolie Records in 1961and the following he appears in Charters film 'The Blues'.
Lightnin' tours Europe in 1964 with the American Folk Blues Festival and he is the subject of Les Blank's short film 'The Blues According to Lightnin' Hopkins in 1967.
Lightnin' make his second and final visit to Europe in 1977, playing dates in Germany and the Netherlands.
Lightnin' Hopkins dies of cancer in Houston on 30 January 1982.