Pozuelo made his official debut with the main squad on 2 October 2011, playing the second half of a 1–0 La Liga home loss against Levante UD.[7] On 18 December he scored his first league goal for the Verdiblancos, as well as being sent off in the 2–0 win at Atlético Madrid.[8]
Pozuelo was promoted to Betis' first team for the 2012–13 campaign.[9] He appeared in a total of 13 games in all competitions, netting his only goal in a 5–3 away victory over Athletic Bilbao.[10]
In total, Pozuelo made 33 appearances during his tenure, scoring three goals.[6]
Swansea City
On 2 July 2013, Pozuelo joined Swansea City on a three-year contract for an undisclosed fee, signing alongside teammate José Cañas and becoming the seventh Spaniard in the squad.[11] He scored on his debut for the club, rounding off the scoring in a 4–0 home defeat of Malmö FF in the first leg of the third qualifying round of the UEFA Europa League.[12] He netted his second in the same competition and also at the Liberty Stadium on 22 August 2013 in a 5–1 play-off round win against Romania's FC Petrolul Ploiești.[13]
During his spell in Wales, Pozuelo played 36 matches across all competitions, scoring twice and adding six assists.[6][14]
Rayo Vallecano
Pozuelo returned to his country's top division on 24 July 2014, joining Rayo Vallecano for an undisclosed fee.[15] His first competitive appearance took place on 14 September, as he came on as a 61st-minute substitute in a 3–2 home loss to Elche CF.[16]
On 31 August 2015, Pozuelo moved abroad again, signing a two-year deal at Belgian Pro League team K.R.C. Genk.[18] He scored six goals in 2016–17, helping to a final eighth position in the regular season. He later became their captain,[19][20] and collected a total of 175 appearances in all competitions over five seasons, with 25 goals and 60 decisive passes.[6]
In February 2019, Toronto FC planned to trigger Pozuelo's €8 million release clause, however, a disagreement ensued with Genk questioning the validity of the release clause and refusing to allow the player to move. Following a lengthy transfer discussion, the two sides reached a compromise for the player to finish out the main portion of the season with the latter and join the former on 18 March.[21] When he left, his team were sitting in first place in the domestic league.[6][22]
On 23 October 2019, Pozuelo scored twice in a 2–1 win over New York City FC in the playoffs' Eastern Conference semi-finals, including a 90th minute Panenka-style penalty kick which was his third of the campaign in that fashion.[29][30] On 10 November, he set up Altidore's injury-time goal in a 3–1 away defeat to Seattle Sounders FC in the MLS Cup Final.[31]
Pozuelo started every match during the 2020 campaign, scoring nine goals and recording ten assists (the joint most in the league) as he led his side to the second best record in the regular season. He was named to the Best XI for a second consecutive year,[32] and on 7 December was awarded the Landon Donovan MVP Award for the league's best player.[33] On 2 July 2022, he played his 100th official match, a 2–0 home loss against Seattle Sounders.[34]
Inter Miami
On 7 July 2022, Pozuelo was traded to Inter Miami CF for $150,000 in General Allocation Money as well as additional conditional GAM depending on certain performance metrics.[35] On 14 August, his brace helped the hosts to defeat New York City 3–2.[36]
Konyaspor
On 3 March 2023, Pozuelo agreed to a short-term deal at Turkish club Konyaspor.[37] On 16 May, he scored twice in a 3–0 win away at Alanyaspor, his second goal being the team's 900th in the Süper Lig.[38]
A versatile and creative midfielder with good ball skills, technique and an eye for goal, Pozuelo usually played in a playmaking role as an attacking midfielder, although he also featured as a central midfielder. Although naturally right-footed, he was capable of playing off of either foot, and is known for his vision and ability to provide assists for teammates. Toronto FC president Bill Manning described him as "a guy who can pull the strings, someone who can manage the game, make the special plays that make goals", while the club's manager Greg Vanney described him as "an attacking player first and foremost. We want to use him in that role. He'll play close to [Altidore] and we'll use him a lot in setting up our attacks. He's outstanding at understanding how to move around, manipulate numbers on the field, play between lines. [He has] the vision for the final pass and the ability to spring some of our guys as runners. But it's also his ability to finish plays off in different ways. For us it's the engine through that final phase of our attack."[21][24][41][42][43][44][45][46][47]