On 14 January, Ramos reportedly took four pain killer injections to his left knee to play against Athletic Bilbao in the
2020–21 Supercopa de España semi-final which Real Madrid went on to lose 2–1.
[147] This was the last match Ramos would play before opting for a mid-season surgery for the first time in his career for a torn meniscus in his left knee.
[148] He was expected to be out for two months and to return in early April, but after a speedy recovery, Ramos started against
Elche on 13 March – just over a month after he went under the knife.
[149] Real Madrid's 2–1 win over Elche was Ramos' 334th La Liga win (315 with Real Madrid and 19 with Sevilla), equalling the record of Iker Casillas as the players with second–most wins in the Spanish top flight – only behind Messi.
[150] Four days later, Ramos played in a Champions League round of 16-second leg for the first time in three years as Real Madrid went on to defeat
Atalanta 3–1 at the Alfredo di Stefano (5–3 on aggregate) and qualified for the quarter-finals for the first time since their last Champions League winning campaign in 2018. Ramos scored his 19th consecutive penalty for Madrid in the 60th minute which killed the game, before coming off as a substitute.
[151] This was Ramos' 15th Champions League goal, equalling former teammates
Gerard Piqué and
Iván Helguera as the second highest scoring defenders in the history of the competition – with only former teammate
Roberto Carlos ahead of them.
[152] Due to an injury, Ramos missed his first El Clásico since joining Los Blancos, putting an end to a streak of playing in 31 consecutive league Clásicos.
[153] He later missed the second leg of the Champions League quarter-finals against Liverpool, as he tested positive for
COVID-19, although he was also injured.
[154] On 5 May, in the Champions League semi-final second leg against
Chelsea, his side lost 2–0 and were eliminated from the competition; however, he then sustained an injury in his left
hamstring which forced him to miss the rest of the season; this meant he had played his last game for Real Madrid.
[155] Ramos played just 21 matches for Los Blancos in 2020–21, making it his most injury-riddled season, after having played at least 33 matches in each of his previous 15 campaigns at the club.
[156]