Goff entered the season with a new head coach in Sean McVay. During Week 1, he completed 21-of-29 passes for 306 yards and a touchdown in a 46–9 win over the Indianapolis Colts. Goff's performance against the Colts marked his first career game with at least 300 passing yards. In Week 3 against the San Francisco 49ers on Thursday Night Football, Goff completed 22-of-28 passes for 292 yards and three touchdowns, leading the Rams to a narrow 41–39 win over the 49ers. In Week 4 against the Dallas Cowboys, Goff completed 21-of-36 passes for 255 yards and two touchdowns as the Rams won 35–30. In Week 5 against the Seattle Seahawks, Goff notably struggled as he had two interceptions, no touchdowns, 288 yards, and a 46.8 completion percentage for a 48.9 passer rating as the Rams lost 10–16. In Week 6, Goff only threw 124 yards and a touchdown to tight end Gerald Everett against the Jacksonville Jaguars in the Rams 27–17 victory despite having an 86.2 passer rating. In Week 7 against the Arizona Cardinals at Twickenham Stadium, Goff passed for 235 yards, a touchdown, and an interception, as the Rams shutout the Cardinals 33–0. During Week 9 against the New York Giants at MetLife Stadium, Goff finished with 311 passing yards and four touchdowns as the Rams won by a score of 51–17, earning him NFC Offensive Player of the Week. During Week 10 against the Houston Texans, Goff finished with 355 passing yards and 3 touchdowns as the Rams won 33–7. In the game, he threw a 94-yard touchdown pass to Robert Woods. During Week 12 against the New Orleans Saints, Goff finished with 354 passing yards, 2 touchdowns, and an interception as the Rams won 26–20. In Week 14, Goff played against the Philadelphia Eagles, going up against 2016 2nd overall pick Carson Wentz. Although passing 16-of-26 attempts, 199 yards, and two passing touchdowns, he fumbled the ball in the last minute, resulting in a 43–35 loss. Goff, even though only throwing for 120 yards, completing 14-of-21 attempts, and two touchdowns in Week 15 against the Seahawks, his team would still win in a huge 42–7 victory. During Week 16 against the Tennessee Titans, Goff finished with 301 passing yards and 4 touchdowns as the Rams won 27–23 and clinched the NFC West for the first time since 2003. Goff sat out Week 17 as a result of this.

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