Weeden was the starting quarterback at Edmond Santa Fe High School, where he led the team to the state semifinals and was named team MVP and offensive player of the year. He finished 2nd in the state of Oklahoma in passing yards with 2,863 and accounted for 25 touchdowns. He was named All-State in football and later that year was also named All-State in baseball. Weeden graduated from Edmond Santa Fe High School in 2002.
