Born in Madrid,[5] Manquillo started playing football with hometown's Real Madrid alongside his twin brother Víctor, a forward. However, in mid-2007, the club decided to release the latter and the former followed suit, with both signing for neighbouring Atlético Madrid 48 hours later.[6]
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). Later, after both went for an aerial challenge, he fell headfirst to the ground,[14][15] going on to be sidelined for more than one month with a neck injury.[16]
Manquillo joined Premier League club Liverpool on 6 August 2014 on a two-year loan with an option to buy after his first season.[17][18] He made his debut 11 days later, playing the full 90 minutes in a 2–1 Premier League victory over Southampton.[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.[20] The following week, in the third round of the Football League Cup, he converted his penalty shoot-out attempt against Middlesbrough as his team prevailed 14–13 following a 2–2 draw.[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.[23]
Manquillo returned to the Premier League on 25 August 2016, joining Sunderland for the whole season.[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.[28] In his final game on 21 May, he scored his first career goal to open the scoring after three minutes at Chelsea, who won 5–1.[29]
Newcastle United
On 21 July 2017, Manquillo signed for Premier League club Newcastle United on a three-year contract for an undisclosed fee,[30] reported by the local Evening Chronicle to be £4.5 million; he was signed by compatriot manager Rafael Benítez.[28] He made his debut on 13 August as the season began with a 2–0 home loss to Tottenham Hotspur.[31]
Manquillo signed a new contract on 25 June 2020, tying him to St James' Park until 2024.[32] He scored his first goal on 11 September 2021, in a 4–1 league loss away to Manchester United.[33]
On 21 January 2024, Manquillo joined Celta Vigo on a one-and-a-half-year contract for an undisclosed fee[34] after failing to make a senior appearance for Newcastle United in the Premier League up until that point in the 2023–24 season,[35] At Celta Vigo, he reunited with manager Rafael Benítez, who had signed him for Newcastle United. He made his debut on 4 February in a 3–0 win over Osasuna, being subbed after 73 minutes.
^Ortega, Alberto (12 February 2014). "Manquillo, un mes con collarín" [Manquillo, one month with neck brace]. Marca (in Spanish). Madrid. Retrieved 14 February 2014.