A survivor of the Holocaust, he devoted himself to battling anti-Semitism, and to track down Nazi war criminals.

In journalist/author Guy Walters's book "Hunting Evil", which is about the efforts to bring escaped Nazi war criminals to justice, Walters is highly critical of Simon Wiesenthal. In the book, Walters describes Wiesenthal as a continuous liar who made up stories about his experiences in World War Two, his Nazi-hunting, and his academic career. Walters also says that the oft-repeated claim that Wiesenthal helped bring over 1,100 Nazis to justice is a massive exaggeration, and that the real number "is in fact probably lower than a dozen".

Laurence Olivier based his performance as the Nazi hunter Ezra Lieberman in The Boys from Brazil (1978) on Wiesenthal.

Awarded an honorary knighthood by the British government in April 2004.