He made over 125 appearances in England's Premier League with Liverpool, Sunderland and Newcastle United, and reached the Coupe de France final with Marseille in 2016.

[13] On 11 February 2014, in the first half of the Spanish Cup semi-final clash against Real Madrid, Manquillo was involved in two incidents with Cristiano Ronaldo: in the early minutes, he conceded a penalty which the Portuguese converted in the first goal of an eventual 2–0 win (5–0 aggregate).

[19] On 16 September, he won a 93rd-minute penalty in the UEFA Champions League tie against Ludogorets Razgrad, which Steven Gerrard converted to make the score 2–1 and win the match.

[21] After featuring in 16 matches during the first part of the season, he played just three times in 2015, never in the domestic league,[22] and Atlético Madrid subsequently confirmed that the loan deal had been terminated.

[26][27] He had what he described as a difficult season on a personal basis, while the Wearsiders were relegated; he totalled 22 appearances and had a clause that would make his transfer permanent for £9.5 million were he to play 25 games.

[33] Manquillo's playing time became limited following the signing of England international Kieran Trippier, resulting in only 4 substitute appearances in the 2022-23 Premier League season.