1. [mid-17C; 19C+] a fool, a stubborn person [on model of ass n.].
2. [20C+] any small motor-powered vehicle.
3. as a form of alcohol [the alcohol ‘kicks like a mule’].
(a) [1910s+] (US) homemade bourbon made from grain alcohol.
(b) [1950s] (US drugs) marijuana soaked in bourbon.
4. in drug uses.
(a) [1920s+] (drugs) a carrier of drugs, typically across international borders, and in many cases an otherwise ‘innocent’ person who has no other contact with the drugs trade.
(b) [1930s+] a drug runner, operating within a given city or prison; on a local scale, the runner who brings supplies from an adjacent hiding place to a street dealer as demand requires.
(c) [1960s+] (US prison, also packhorse) a smuggler, usu. a visitor or prison warder.
(d) [1990s+] any form of carrier, e.g. of weapons for a gang.
5. [1920s+] (US) the penis [earlier cits. are doubles entendres].
6. [1940s+] as a derog. description.
(a) an unattractive woman.
(b) (US campus) an unattractive man.
(c) an impotent man.
(d) (W.I.) an infertile woman, who therefore suffers from mule-belly.
7. [1960s] (US) vodka.
[1920s–60s] (US) illicitly distilled corn whisky.
[1900s–10s] (US) corn whisky or gin.
[1950s+] (US) to masturbate.
[1990s+] to have sexual intercourse.
SE in slang uses
[1920s–40s] (US) a straw hat.
[1970s] (US) of a man, to copulate aggressively, violently.
[1970s+] (US black) one who works regularly as a police informer.
[late 19C–1920s] (US) a mule-driver.
[mid-19C] (US) a nonsensical phr. used by troops during the US Civil War.
[1920s+] (US) a mild oath, used to express disbelief or surprise.