[6][7] He was promoted to the first team for 2011–12 as third-choice – still continuing to appear for the B's – but suffered a severe injury to his cruciate ligaments in November that kept him out of action for five-and-a-half months.

[11] Following his debut, he went on to start the next 31 matches, keeping 11 clean sheets as the club finished in seventh place and qualified for the UEFA Europa League.

[12][13] Having been watched playing for Betis by West Ham United manager Sam Allardyce and goalkeeping coach Martyn Margetson, Adrián was persuaded to join the club.

[22] On 11 February 2015, Adrián was given a straight red card in a goalless draw at Southampton for handling the ball outside the penalty area while pressured by Sadio Mané.

[26] Adrián received a straight red card in added time at the end of West Ham's 1–2 home loss to Leicester City on 15 August 2015 for a high challenge on Jamie Vardy, after going up for a corner kick.

He had played 150 in all competitions for West Ham but only five in his final season, all cup games, as his place in their Premier League team was taken by Łukasz Fabiański.

[33] On 14 August, Adrián started in the 2019 UEFA Super Cup; in extra-time, he conceded a penalty for a foul on Tammy Abraham, from which Jorginho was able to tie the match for Chelsea.

Although he made a remarkable save from Belgian international Dries Mertens when the game was scoreless, Adrian fell to his first defeat as a Liverpool player on a 2–0 scoreline.

[39] Due to the unavailability of first and second choice goalkeepers Alisson Becker and Caoimhín Kelleher, Adrián played in the 2022 FA Community Shield in July 2022 against Manchester City which Liverpool won 3–1.

[44] On 26 August 2016, Adrián received his first call-up to the senior Spain squad by new manager Julen Lopetegui for matches against Belgium and Liechtenstein.