Karius would go on to play in the 2018 UEFA Champions League final with the club, suffering a 3–1 defeat to Real Madrid.

[7] Manchester City invited Karius and his family to England after watching him in Germany's under-16 game against Azerbaijan, and completed his signing on 1 July 2009.

On 11 January 2012, the move was made permanent with Karius committing himself to a two-year deal with an option for a third year that would extend his contract to June 2015.

[13] Karius was ever-present in the 2015–16 season, keeping nine clean sheets, saving two penalties and being voted the second-best goalkeeper in the league in a poll of 235 fellow Bundesliga players, ranking behind only Manuel Neuer.

[20] Karius recorded his first Premier League clean sheet on 17 October, in a 0–0 draw with rivals Manchester United.

[21] On 24 October 2016, Jürgen Klopp confirmed that Karius was Liverpool's first-choice goalkeeper, ahead of Simon Mignolet.

[22] After two sub-par performances in early December, which included spilling Lewis Cook's tame shot into the path of Nathan Aké to tap home into an empty net to give Bournemouth a 4–3 win, Karius was dropped from the starting eleven.

"[23] In the 2018 Champions League quarter-final second leg away to Manchester City, with the aggregate scoreline at 3–1 to Liverpool, Karius was involved in a controversial incident when he failed to clear a cross into the penalty area, punching the ball down which ricocheted off teammate James Milner and into the path of City winger Leroy Sané who scored, only for the linesman to give offside.

[27] He was deemed at fault for two of the goals that Liverpool conceded, the first and third: the first when his throw was blocked by Karim Benzema and deflected into the net; the second when he mishandled Gareth Bale's 40-yard strike.

[30] After the match, Karius received online death threats, mainly on Twitter, which prompted Merseyside Police to launch an investigation.

[41] In March 2019, he sought legal action against Beşiktaş for back payment of four months' wages which he alleged the club had failed to pay him.

[42] On 4 May 2020, Karius terminated his contract with the Turkish outfit due to continuing issues regarding unpaid wages and after completing the majority of the two years agreed.

[49] However, manager Jürgen Klopp stated in January 2022 that Karius would not be included in the squad; he made no further official appearances for the club until the end of his contract.

[59] Karius represented Germany at all youth levels from under-16 onward, but his appearances were limited due to competition from other goalkeepers.