Carradine's first film credit was Tol'able David (1930), but he claimed to have done 70 pictures before getting billing. Carradine claimed to have tested, as an unknown – along with well-known leading men Conrad Veidt, William Courtenay, Paul Muni, and Ian Keith – for the title role in Dracula, but the historical record does not support the claim. The part eventually went to Bela Lugosi. Carradine would later play the Count in the 1940s Universal Studios Dracula sequels House of Frankenstein and House of Dracula. Carradine also claimed to have tested for the monster role in Frankenstein (1931), though again, no account exists other than his own that he actually did so. By 1933, he was being credited as John Peter Richmond, perhaps in honor of his friend, John Barrymore. He adopted the stage name "John Carradine" in 1935, and legally took the name as his own two years later. In 1935's Bride of Frankenstein, Carradine had a brief uncredited walk on role as a hunter in the forest.
Carradine was married four times. He married his first wife, Ardanelle Abigail McCool (January 25, 1911 – January 26, 1989), in 1935. She was the mother of Bruce and David. John adopted Bruce, Ardanelle's son from a previous marriage. John had planned a large family, but according to the autobiography of his son David, after Ardanelle had had a series of miscarriages, Carradine discovered that she had had repeated "coat hanger" abortions, without his knowledge, which rendered her unable to carry a baby to full term. After only three years of marriage, Ardanelle Carradine filed for divorce, but the couple remained married for another five years.