Locke's next game was his best of the 1921 season. He carried the ball 37 times and gained a school-record 202 yards rushing in a 14–2 victory over Illinois. Locke scored both Iowa touchdowns. However, he was soon hospitalized with stomach problems, which hampered his effectiveness the rest of the year. Still, Locke finished the 1921 season with over 700 rushing yards and finished second in the Big Ten Conference scoring race to teammate, Aubrey Devine. Iowa posted a perfect 7–0 record in 1921 and won its first Big Ten title in 21 years. Locke was a consensus first team All-Big Ten selection and a first team All-American in 1921.