On April 6, 2022, Diggs signed a four-year, $96 million contract extension with the Bills through the 2026 season. In Week 1 against the Los Angeles Rams, Diggs caught eight passes for 122 yards, and had a 53-yard touchdown in the fourth quarter in the 31-10 win. In Week 2, against the Tennessee Titans, Diggs had 12 receptions for 148 yards and three touchdowns in the 41–7 victory. In Week 5, against the Pittsburgh Steelers, he had eight receptions for 102 yards and a touchdown in the 38–3 victory. In Week 6, against the Kansas City Chiefs, he had ten receptions for 148 yards and one touchdown in the 24–20 victory.
