On 2 July 2018, Arsenal announced that Papastathopoulos had agreed a long-term contract with the club for a reported fee £17.6 million and would wear the number 5 shirt. On 12 August 2018, he made his official debut with the club as a starter at Emirates Stadium, in a 2–0 loss against champions Manchester City. On 4 October 2018, Papastathopoulos scored his first for the club, setting the "Gunners" on their way to a comfortable 3–0 victory over Qarabag in the 2018–19 UEFA Europa League group stage: after just four minutes of play in Baku, the centre-back was left unmarked inside the opposing penalty area, deflecting the ball home after an initial header fell into his path. Papastathopoulos was named to the UEFA Europa League Team of the Week.