Mata had a release clause at Real Madrid during his last season at the club, and eventually agreed to sign for fellow La Liga side Valencia CF in March 2007, with the contract starting on 30 June 2007.

On 1 February 2007, under-21 coach Iñaki Sáez included him on his squad for the friendly against England, alongside Real Madrid teammates Roberto Soldado, José Manuel Jurado, Sergio Sánchez, Miguel Torres, Esteban Granero, and Antonio Adán, at just 18 years and 10 months.

Benefitting from constant injuries to Vicente and the ostracism to which then-manager Ronald Koeman condemned Miguel Ángel Angulo, Mata gradually carved a niche in Valencia’s first eleven. On 20 March 2008, he scored twice in the Copa del Rey semi-final match against FC Barcelona to help Valencia reach the final against Getafe CF where, on 16 April, he netted the opener in a 3–1 win. During that first season, he was voted the team’s Best Young Player by fans and players alike.

In the 2008 Spanish SuperCup, Mata scored against his former club Real Madrid in a 3–2 first leg win, but Valencia lost 5–6 on aggregate after a 2–4 away loss in the second game. He started 2008–09 well, scoring in the opener against RCD Mallorca in a 3–0 win. He also netted the only goal of the game against CA Osasuna, latching on to a long ball from David Villa.

On 25 September 2008, Mata proved to be growing in efficiency, as he set up two of his teammate’s goals in a 2–0 away win over Málaga CF. Three days later, he put in a superb performance against Deportivo de La Coruña, scoring one and creating the other three, in a 4–2 home victory.

On 14 November 2008, Vicente del Bosque called up Mata for the senior team to play in a friendly against Chile. He did not leave the bench in a 3–0 home win. On 28 March 2009, he finally made his debut, playing in the 2010 FIFA World Cup qualifier against Turkey, a 1–0 win in Madrid. He came on as a substitute for teammate David Villa in the 63rd minute.

In June 2009, Del Bosque included Mata for the 2009 FIFA Confederations Cup, the youngster’s first senior tournament. He started in the second group match against Iraq and came on as a substitute for Albert Riera in the semi-final loss to the United States.

On 9 September 2009, Mata scored his first goal for the senior team, as the 3–0 win against Estonia secured a place in the World Cup in South Africa. He followed this up with the winner against Armenia on 10 October, scoring a penalty to steal a 2–1 win. Picked for the final stages, he appeared once for the eventual champions, replacing Fernando Torres for the final 20 minutes of the 2–0 group stage win against Honduras.

In the following two seasons, Mata was an everpresent offensive figure for Valencia, scoring 17 goals in 68 games combined, with the club achieving back-to-back third-league places. On 10 April 2011, he netted two in a 5–0 home win against Valencian neighbours Villarreal CF. On 9 May, England-based Spanish journalist Guillem Balagué reported interest from several Premier League clubs.

On 21 August 2011, Valencia announced they had agreed a £23.5 million fee for the transfer of Mata to Premier League club Chelsea, subject to a medical. On 24 August 2011, Mata signed a five-year deal with Chelsea. He revealed that compatriot Fernando Torres helped persuade him to move to Stamford Bridge, saying “Fernando got me excited about the thought of coming here. He said it would be good for me here, and that me and him together could be good. I also talked to my family and friends about it as well.”

On 26 August 2011, Yossi Benayoun offered Mata his number 10 shirt. The Israeli captain said, “I decided to give Mata the number 10 – his favourite. For me, it’s just a number, not my lucky 15.” (Florent Malouda wore number 15 for Chelsea at the time.) Mata wore number 10 for Valencia and for Spain’s under-21s in the summer, and expressed his gratitude to Benayoun. “It is a very important number to me so I’m pleased to be wearing it. I want to thank Yossi,” he said. Mata followed on from Chelsea players Joe Cole, Mark Hughes, Ian Hutchinson, and Terry Venables in adopting the number 10 shirt.

Mata made his debut for Chelsea against Norwich City on 27 August 2011, where he came on as a 68th-minute substitute for Florent Malouda and scored the club’s third goal in the 11th minute of stoppage time. Chelsea went on to win the match 3–1. He started his first game for his new club in their next fixture on 10 September away to Sunderland, helping Chelsea secure a 1–2 win. On 14 September, Mata made his UEFA Champions League debut for Chelsea and netted in stoppage time to help his side defeat Bayer Leverkusen 2–0.

On 29 October 2011, Mata assisted Chelsea’s 6,000th league goal with an in-swinging cross which was headed in by Frank Lampard. In the same game, Mata scored with a spectacular 25-yard strike in a 3–5 home defeat to London rivals Arsenal. On 26 November, Mata set up the first two goals which were scored by John Terry and Daniel Sturridge and also scored the third goal himself in a 3–0 win against Wolverhampton Wanderers. He was awarded the Man of the Match in a 0–3 away win at St James’ Park for his performance against Newcastle United.

On 6 December 2011, during Chelsea’s decisive Champions League match against former club Valencia CF, Mata created two assists for both of Didier Drogba goals. The game ended in a 3–0 win, which resulted in Chelsea qualifying first from their group. On Boxing Day, Mata scored his side’s only goal in a 1–1 draw at Stamford Bridge against Fulham. Mata scored Chelsea’s first goal of their FA Cup campaign in a 4–0 win over Portsmouth at Stamford Bridge.

In 2011, the following summer, he went back to the under-21 side, playing the role of senior squad member and helped Spain win the 2011 UEFA European Under-21 Championship in Denmark. Mata himself was included in UEFA’s Team of the Tournament and named as the tournament’s Golden Player.

In an FA Cup fourth round tie with Queens Park Rangers at Loftus Road, Mata scored his side’s only goal from the penalty spot in a 0–1 victory. On 5 February 2012, Mata scored against Manchester United in a 3–3 draw. On 21 February, Mata scored his side’s only goal in their 1–3 defeat away at Napoli in the first leg of the Champions League round of 16.

In the 2012 UEFA Champions League Final against Bayern Munich on 19 May, Mata assisted Didier Drogba’s headed equaliser from a corner kick in the 88th minute. The match went on to extra time and penalties, with Mata taking Chelsea’s first, which Bayern goalkeeper Manuel Neuer saved. Chelsea, however, went on to win 4–3 in the penalty-shootout, lifting their first Champions League title. Mata finished his first season at Stamford Bridge with 573 passes, creating 66 chances and completing 61 successful crosses, which all contributed to Chelsea’s cup-double winning season. He finished the Premier League season with 14 assists – second highest in the league after Manchester City’s David Silva – and six goals.

Mata missed all of Chelsea’s pre-season games as he was playing for Spain at the 2012 Summer Olympics in London, but he returned to play in the 2012 FA Community Shield against Manchester City and was substituted after 74 minutes for Daniel Sturridge. Mata assisted his first goal of the season on 22 September 2012 against Stoke City, providing a great flick to Ashley Cole, which turned out to be the winning goal as Chelsea won 1–0. He scored his first goal of the season in the 2012–13 Football League Cup third round against Wolverhampton Wanderers, with the game finishing 6–0 to Chelsea. Four days later, he scored his first Premier League goal of the season, assisting Fernando Torres for the opener and then scoring directly from a free-kick in a 2–1 away win against Arsenal at the Emirates Stadium.

On 22 December 2012, Mata signed a contract extension with Chelsea which tied him up with the club until 2018. On Boxing Day, Chelsea traveled to Carrow Road to face Norwich City, where both Manchester United and Arsenal had suffered defeats earlier in the season. Mata scored a brilliant goal in the 38th minute, taking a pass from Oscar into his stride and launching an unstoppable shot into the goal from 25 yards out. The goal turned out to be the winner. Then, on 5 January, Mata provided assists for new acquisition Demba Ba and Branislav Ivanović to help Chelsea win 1–5 against Southampton in the third round of the 2012–13 FA Cup. A week later, he forced an own goal from Jonathan Walters by putting in a tight corner and earned a penalty which Frank Lampard converted. Chelsea went on to win the game 0–4, which was Stoke’s first home defeat of the season. Mata scored his eighth goal of the season in the Premier League against Arsenal in a 2–1 home win.

In November 2012, along with fellow Premier League players Santi Cazorla and Michu, Mata bought shares in former club Real Oviedo, who were struggling to raise €2 million to stay afloat in the Spanish third division.

On 3 March 2013, Mata made his 100th appearance in all competitions for Chelsea in a 1–0 win over West Bromwich Albion at Stamford Bridge. On 14 March, Mata scored an opening goal in Chelsea’s Europa League 3–1 (3–2) win against Steaua București. On 19 April, Mata was nominated for PFA Players’ Player of the Year in recognition of his contribution to Chelsea’s season in all competitions. The PFA’s decision was based on his “ability to not only create goals but also score them himself” and saw him nominated alongside teammate Eden Hazard. He also netted an 87th-minute winner against Manchester United, a crucial one for Chelsea’s Champions League qualification hopes.

On 15 May, Mata gave a fine performance in the 2013 UEFA Europa League Final against Portugal’s Benfica, assisting Branislav Ivanović’s injury time winner from a corner kick. The next day, he was awarded Chelsea’s Player’s Player of the Year award. He modestly gave the credit to the whole of the squad, saying that, “he felt proud to play for Chelsea,” and thanked his teammates. He was also awarded Chelsea’s Player of the Year for the second successive season. On winning his second award of the night, he said, “I feel so happy. It’s my second season here and winning the trophy two years in a row is amazing for me. I just want to say thank you to all the supporters and all my teammates.”

Under new Chelsea manager José Mourinho, Mata spent a lot of time on the bench. Mourinho preferred Oscar as a playmaker, and suggested Mata needed to adapt to a wider position and to working harder defensively. On 28 September 2013, Mata came on as a half-time substitute against Tottenham Hotspur to assist John Terry to score an equaliser in a 1–1 draw, but his appearances in the first team remained infrequent. On 29 October, he scored his first goal of the season in a 2–0 League Cup victory at London rivals Arsenal.

On 24 January 2014, Mourinho said Chelsea had accepted a transfer offer from Manchester United and he allowed Mata to travel to Manchester to undergo a medical, after the player said he was “really happy to go”. Manchester United confirmed later in the day that a transfer fee had been agreed, but that the deal was still contingent on Mata agreeing personal terms and passing a medical. The transfer was completed the following day, with Manchester United paying Chelsea a then club record fee of £37.1 million (€46 million), with Mata signing a contract until the summer of 2018.

He made his debut against Cardiff City on 28 January and provided one assist in the 2–0 home victory. Mata scored his first goal for United in a 4–1 win over Aston Villa on 29 March 2014. He also went on to score two goals against Newcastle United in a 4–0 away victory, two more against Norwich City after coming off the bench in another 4–0 win, and the only goal in a 1–1 draw against Southampton in the final match of the season.

Following Rooney’s sending off and suspension due to a foul on Stewart Downing in the match against West Ham, Mata was reinstated to the starting lineup, and he started the next match against Everton, a 2–1 win at Old Trafford in which he provided the assist for Ángel Di María’s goal. Mata later scored winning goals in home games against Crystal Palace and Stoke City, the former after coming on as a second-half substitute. He made his return to the starting line-ups for the first time, in a 3–0 win over Tottenham but was substituted in the 77th minute for Andreas Pereira. On 22 March 2015, Mata scored a brace, including a bicycle kick, in a 2–1 victory over Liverpool, a performance which he rated as his best for Manchester United. His second goal against Liverpool was also voted as Premier League Goal of the Month in March 2015. His inspired performances led to him being named as Manchester United’s Player of the Month for March.

On 21 May 2016, Mata scored for United in the FA Cup Final against Crystal Palace, leveling the score at 1–1 just three minutes after Jason Puncheon’s 78th-minute goal. Mata was substituted in the 90th minute and replaced by Jesse Lingard, who would score the winning goal for United in extra time.

At the beginning of the summer, Mata was reunited with his former Chelsea manager and the person who sold him to Manchester United, José Mourinho. On 7 August 2016, Mata was selected to be on the bench in the FA Community Shield. Mata replaced Jesse Lingard in the second half, then was substituted in added time for Henrikh Mkhitaryan. Although there were reports about tensions between the player and manager, after the match, Mata stated that there were no tensions between him and Mourinho. He started in the opening match of the season against A.F.C. Bournemouth and scored Manchester United’s first Premier League goal of the season with a tap-in after Simon Francis’ error.

After José Mourinho dropped captain Wayne Rooney, Mata served as the stand-in captain in the 0–0 draw against Burnley on 29 October 2016.

In August 2017, Mata announced in an article for The Players’ Tribune that he was pledging one percent of his salary to a pledge-based charitable movement, named Common Goal, and called for other football players to do the same.

Mata netted his third brace of his Manchester United career, scoring both goals for the Red Devils in a Boxing Day fixture against Leicester City. However, his efforts were cancelled out by a late equaliser from Harry Maguire which saw the match finish 2–2. Mata finished the season with three goals in 40 appearances for the Red Devils, as United finished second in the Premier League and lost in the 2018 FA Cup Final against his former club, Chelsea.

Mata scored United’s first goal of the season in a friendly against Club América on 19 July 2018. Mata’s first competitive goal can in the 3rd minute of United’s League Cup exit to Derby County on 25 September 2018. On 6 October, Mata scored United’s first goal in a 3-2 comeback win over Newcastle United. Later, on 7 November 2018, Mata scored the equaliser from a free kick in another late comeback 2–1 win over Juventus in a Champions League group stage fixture. Mata also scored in a 4–1 win over Fulham on 8 December 2018, before scoring his final goal of the season in a 1–1 draw against his former club Chelsea on 28 April 2019.

On 19 June 2019, it was confirmed that Mata had signed a new two-year contract with Manchester United, keeping him at the club until June 2021 with the option of a further year. This ended months of speculation over his future.