Slander at first, most unfair detraction (3)
I believe the answer is:
mud
'slander' is the definition.
(mud is a kind of slander)
'first most unfair detraction' is the wordplay.
'first' says to take the initial letters.
The initial letters of 'most unfair detraction' is 'MUD'.
'at' acts as a link.
(Other definitions for mud that I've seen before include "in your eye, it's an affable toast" , "Wet soil" , "Clay" , "Mire" , "slander" .)