On 21 June 2017, having narrowly avoided relegation the previous season, Hamburger SV signed Papadopoulos on a permanent three-year deal from Bayer Leverkusen on a €6.5 million transfer fee, with the "Dinosaurs" to offer another €3 million in the form of a target bonus, for the next three years. On 9 August 2017, despite having been with the club for only six months, he was named vice-captain for the 2017–18 season. On 12 December 2017, he scored his first goal for the season in a 2–1 home loss against Eintracht Frankfurt.