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For the scene where Angel Eyes interrogates Maria the prostitute for information about Bill Carson, Lee Van Cleef was appalled by the fact that he was required to actually hit Maria (Rada Rassimov), complaining "I can't hit a woman." Rassimov replied with, "Don't worry. I'm an actress. Even if you slap me for real, it's no problem", but Van Cleef further stated, "I know, but I can't!" As a result, a stunt double was used for shots where Rassimov was slapped, which were intercut with shots of Van Cleef. As he later put it: "There are very few principles I have in life. One of them is I don't kick dogs, and the other one is I don't slap women in movies."
According to Eli Wallach, when it came time to blow up the bridge, Sergio Leone asked the Spanish Army Captain in charge to trigger the fuse, as a sign of gratitude for the Army's collaboration. They agreed to blow up the bridge when Leone gave the signal "Vai!" (Go!) over the walkie-talkie. Unfortunately, another crew member spoke on the same channel, saying the words "vai, vai!", meaning "it's okay, proceed" to a second crew member. The Captain heard this signal, thought it was for him, and blew up the bridge. Unfortunately, no cameras were running at the time. Leone was so upset that he fired the crewman, who promptly fled from the set in his car. The Captain was so sorry for what happened that he proposed to Leone that the Army would rebuild the bridge to blow it up again, with one condition: that the fired crewman be re-hired. Leone agreed, the crewman was forgiven, the bridge was rebuilt, and the scene was successfully shot.
Because writer and director Sergio Leone spoke barely any English and Eli Wallach (Tuco) spoke barely any Italian, the two communicated in French.
Clint Eastwood wore the same poncho through all three "Man with No Name" movies without replacement or cleaning.
In the gun store, everything Tuco ( Eli Wallach ) does with the guns was unscripted. Wallach knew little about guns, so he was instructed to do whatever he wanted. He did receive instruction, however, on how to disassemble and assemble them. Most of the Storekeeper's (Enzo Petito's) bemused reactions throughout the scene are genuine. The scene where Tuco shoves the open or closed sign in his mouth was also Wallach's idea.
Eli Wallach was almost poisoned on the set after drinking acid used to burn the bags filled with gold coin, to make them rip open easier when struck with the spade. He didn't know the acid had been poured into a lemon soda bottle. He drank a lot of milk, and filmed the scene with a mouth full of sores.