There have been several reasons stated publicly, but the main reason was Eastwood’s dislike of the extremely long set-up process Director Leone employed to get the shots he wanted, of which he did the most when Eastwood worked on the epic western, “The Good, The Bad, & The Ugly” (1966). Despite having become a star via Leone, Eastwood considered the process not only tedious, but time & budget wasteful, he was also unhappy about the lesser screen time he got on said 3rd film, as opposed to co-star Eli Wallach (Leone thought little of Eastwood’s actual acting chops). So when he was offered the part of “Harmonica” in Leone’s subsequent western, “Once Upon A Time In The West”, keenly aware that the very same process by Leone would not only be used, but then some, he declined.
Ironically, his experience working with Leone (seen on left in below pic with Eastwood) & on other film productions over the years, was a contributing factor as to why Eastwood formed his own film production company “Malpaso”, with the very streamlined process he employs when making his own films.