Beginning his career at his hometown club of Wil, Schär transferred to Basel in 2012, winning the Swiss Super League in all three of his seasons there before his move to TSG Hoffenheim.

[5] He scored his first goal for his new club on 7 October in the St. Jakob-Park during the 3–2 home win against Servette, heading an equaliser following a corner from Fabian Frei.

Schär scored his first goals for Newcastle against Cardiff City on 19 January 2019, netting twice in a 3–0 victory at St James' Park.

[20] On 4 October 2023, Schär scored his first Champions League goal for Newcastle United against Paris Saint-Germain in a 4–1 home victory during the 2023–24 season group stage.

He scored his first goal for the Swiss U-21 during his fourth appearance for them on 10 September 2012 in a match against Estonia U-21[24] This was the final game in the qualification to the 2013 UEFA European Under-21 Football Championship.

In the first leg of the qualification play-offs on 12 October 2012 against the German U-21 team Schär was shown the red card after he fouled Sebastian Polter as last man.

[28][29] On 6 September 2013, Schär made both his first competitive appearance and full debut for Switzerland in a 2014 FIFA World Cup qualifier against Iceland.

[31] He started a third consecutive match in the away qualifier against Albania on 11 October, as the Swiss won 2–1 to ensure qualification for the tournament finals in Brazil.

[33] He made his tournament debut as a starter in the team's third match, replacing the injured Steve von Bergen and helping Switzerland to a clean sheet in a 3–0 defeat of Honduras.

[35] During UEFA Euro 2016 qualifying, Schär scored twice and provided four assists as the team finished second in Group E to reach the tournament finals in France.

[37] He was an ever-present in central defence for the Swiss during the tournament, helping to shut out host nation France in the final Group A match, earning the team a 0–0 draw which qualified them for the knockout stage.

[38] In the round of 16 match against Poland, Schär played the full 120 minutes and was one of four Swiss players to score in the penalty shootout.

[39] He was included in the 23-man squad for the 2018 FIFA World Cup[40] and played in all three Group E matches as the Swiss reached the knockout stage with an unbeaten record against Brazil, Serbia and Costa Rica.

Due to receiving two yellow cards in the group stage, Schär was suspended for the round of 16 match against Sweden, which the Nati lost 1–0.