It is located on the site of the Jewish town Sikhnin (or Sikhni), which flourished during the Roman conquest (2nd century CE).
During the 1948 Arab-Israeli war, Sakhnin surrendered to Israeli forces on July 18, 1948, during Operation Dekel, but was re-captured by Arab forces shortly afterwards. It finally fell without battle into Israeli hands in October 1948.
In 2003, Sakhnin's team, Bnei Sakhnin, became one of the first Arab teams to play in Israel's top soccer league.