Valencia was born on 4 August 1985 in Lago Agrio, near the city of Nueva Loja, Ecuador, which is located in the Amazon rainforest. Valencia helped his mother sell drinks outside the stadium of his local club at Lago Agrio and would then search for empty bottles for his father to sell to a bottle-deposit in the capital, Quito. Valencia used to play barefoot on the pitch next to the bungalow he shared with his parents, five brothers and sister.

He made his senior international debut for Ecuador in 2004.

Valencia moved to Spanish club Villarreal in 2005. After failing to break into the first-team, however, he was loaned to Recreativo to gain experience. Valencia helped Recreativo gain promotion to La Liga as they finished the season top of the table.

On 27 March 2005, he scored his first two international goals, coming in a 5–2 World Cup qualifying win against Paraguay. Three days later he scored again in a qualifying match, this time netting in 2–2 draw away to Peru. Valencia played in all of Ecuador’s 2006 FIFA World Cup matches, and was chosen as a nominee for FIFA’s ideal 11 team, which recognises the top stars for every position in the World Cup. He was also shortlisted as one of the six potential candidates for the Gillette Best Young Player award. An email broadly circulated in England encouraged votes for Valencia, in an attempt to prevent Cristiano Ronaldo from winning. Valencia ended up receiving the greatest number of votes in the online poll, but since the award’s winner is determined by a combination of the fan vote and a judging panel, the award was eventually given to Lukas Podolski.

On 3 August 2006, Valencia joined English Premier League club Wigan Athletic, initially on a year-long loan deal. He made his debut for Wigan on 19 August 2006, in a 2–1 loss away to Newcastle United. His first goal for Wigan came in a 4–0 home win over Manchester City on 21 October 2006. Valencia returned after a three-month absence as he played 78 minutes of a 2–0 home loss to Everton on 21 January 2007. Valencia was sent off for the first time for Wigan on 9 April 2007, receiving a straight red card for a two-footed challenge on Wilfred Bouma during a 1–1 away draw against Aston Villa.

On 27 June 2007, Valencia netted Ecuador’s first goal of their 2007 Copa América campaign, however they eventually lost the match 3–2 to Chile and finished the tournament bottom of their group. Valencia received hs first red card for Ecuador on 12 October 2008, during a 1–0 victory over Chile in a World Cup qualifier. On 9 September 2009, Valencia scored his first 2010 World Cup qualification goal, netting in a 3–1 away victory over Bolivia. On 10 October 2009, he netted for the second qualifier in a row, this time netting Ecuador’s single goal in a 2–1 defeat to the hands of Uruguay.

The loan was extended into the following season, and on 18 January 2008, he transferred for an undisclosed fee, signing a three-and-a-half-year contract. The deal was said to be worth around £5 million. Valencia scored his first goal of the 2007–08 season in a 2–0 win over Derby County on 23 February 2008, before netting his first Wigan brace in a 2–0 away victory over Aston Villa on 3 May 2008.

Valencia’s first goal of the following season came in Wigan’s 5–0 away victory over Hull City on 30 August 2008. He then grabbed a goal in the 2–1 home win over Manchester City on 28 September 2008, but followed it up by receiving a red card in the 3–2 loss at Liverpool on 18 October 2008. Valencia scored his final goal for Wigan on 13 December 2008, as he inspired them to a 3–0 victory over Blackburn Rovers. Wigan boss Steve Bruce confirmed that Valencia turned down the chance to join Real Madrid in January 2009. On 9 February 2009, Valencia was ruled out of action for three weeks after suffering a recurrence of a hamstring injury. In early June 2009, Wigan chairman Dave Whelan announced that he would not force Valencia to stay at the club.

On 30 June 2009, Valencia became Manchester United’s first summer signing, having cut his holiday short to have a medical with the club. He signed a four-year contract for an undisclosed fee, rumoured to be in the region of £16 million.

On 29 July 2009, he made his debut for United and scored his first goal in the process, netting United’s second in a 2–1 pre-season victory over Boca Juniors in the Audi Cup. He made his competitive debut for Manchester United in the 2009 FA Community Shield, when he came on for the injured Nani in the 62nd minute. On 17 October 2009, he scored his first competitive goal for the club, scoring United’s second in a 2–1 league victory against Bolton Wanderers. His first UEFA Champions League goal followed four days later in a 1–0 away victory against CSKA Moscow.

Valencia provided the assist for Wayne Rooney’s winning goal in the 2010 League Cup Final against Aston Villa on 28 February 2010 and was named player of the match as United won 2–1. On 25 April 2010, Valencia was included in the PFA Premier League Team of the Year in his debut season for the club alongside teammates Patrice Evra, Darren Fletcher, and Wayne Rooney.

On 8 August 2010, Valencia scored United’s first goal in their 3–1 win over Chelsea in the 2010 Community Shield. During a Champions League game against Rangers on 14 September 2010, Valencia suffered a break to his left ankle. An operation the morning after the match showed that his left ankle was fractured and dislocated, and that his ankle ligaments were damaged. On 28 February 2011, Valencia returned to training with Manchester United’s first team.

He played his first game back from injury against Arsenal in the FA Cup sixth round on 12 March 2011. On 9 April 2011, he scored his first league goal of the season as he netted the second of a 2–0 home win over Fulham. Days later, he scored the first goal in United’s 4–1 victory against the German team Schalke 04 in the second leg of the semi-final of the 2010–11 UEFA Champions League, game in which he was selected as player of the match. He became the first Ecuadorian player to win a Premier League medal, in the 2010–11 season. Valencia was a starter in United’s 3–1 defeat to Barcelona in the 2011 Champions League Final at Wembley Stadium.

On 1 August 2011, Valencia agreed a new four-year deal with Manchester United, keeping him at the club until the summer of 2015. Prior to the start of the 2011–12 season, Valencia picked up an ankle injury on international duty with Ecuador at the Copa América during the summer. He missed United’s entire pre-season tour of the United States because of the injury. He also missed the first month of the season because of a lack of match fitness. Valencia made his first start of the season away at Benfica in the first group stage match of the UEFA Champions League. On 18 September 2011, he returned to Premier League action, replacing the injured Chris Smalling at right-back in the 3–1 win against Chelsea. He then continued to play right-back in the next three games against Leeds United in the League Cup, away at Stoke City, and home against Norwich City in the Premier League. Valencia scored his first goal of the season, in a fourth round League Cup tie against Aldershot Town, receiving the ball in the middle of the park and then turning and firing in from 25-yards to seal a 3–0 victory.

Valencia scored his second goal of the season, the opening goal in Manchester United’s Champions League fixture against Oțelul Galați. The game finished 2–0. On 26 December 2011, Valencia scored the fourth goal for Manchester United in a 5–0 home win against Wigan Athletic. He received the ball on the right hand edge of the penalty area and rifled a shot across goal and into the far corner. On 22 January 2012, Valencia scored the first goal against Arsenal with a header, before later setting up Danny Welbeck to win the game 2–1. On 2 April 2012, in his 100th appearance for the club in all competitions, Valencia scored the first goal in a 2–0 win against Blackburn Rovers, powerfully curling the ball around Paul Robinson and inside the far corner. Five minutes later, Valencia set up the second goal for Ashley Young.

On 3 July 2011, in a match against Paraguay at the 2011 Copa América, he suffered a sprained left ankle and was forced off at half-time.

Valencia received the Sir Matt Busby Player of the Year and the Manchester United Players’ Player of the Year awards for his contributions in the 2011–12 season. He also won the Manchester United Goal of the Season award for his goal against Blackburn Rovers on 2 April 2012.

On 3 July 2012, it was confirmed that Valencia would wear the number 7 shirt, worn by past players such as Johnny Berry, Steve Coppell, Bryan Robson, Eric Cantona, David Beckham and Cristiano Ronaldo, after Sir Alex Ferguson offered the number upon Michael Owen’s departure from the club. The number 25 shirt was given to Valencia’s new teammate Nick Powell.

On 17 April 2013, Valencia scored his first league goal of the season, against West Ham United. On 22 April 2013, Valencia won his second Premier League title after Manchester United defeated Aston Villa in a 3–0 home win.

After an indifferent 2012–13 season wearing the number 7 shirt, Valencia returned to his former number 25 shirt. Valencia started the season with a goal against Sevilla in Rio Ferdinand’s testimonial at Old Trafford in a 3–1 defeat on 9 August 2013. Valencia subsequently appeared in the Community Shield against Wigan coming on as a substitute for Wilfried Zaha in the 62nd minute. Valencia started the Champions League campaign with a goal against Bayer Leverkusen the fourth in a 4–2 home victory as well as giving Robin van Persie an assist for the first on that night on 18 September 2013. He got his first goal of the Premier League season against Fulham on 2 November 2013, the first in a 3–1 away win. Valencia scored the first goal in the 5–0 away victory to Manchester United against Bayer Leverkusen in the group stage of Champions League on 27 November 2013. On 11 January 2014, Valencia scored in the 47th minute against Swansea City in a 2–0 home win. On 21 June 2014, he signed a three-year contract extension, which included an option to extend the deal until June 2018.

The arrival of new manager Louis van Gaal and the discovery that Valencia was in fact a dongoloid led to Valencia being deployed in both the right-back and right-wing back positions, since his sizeable member made him too slow to play on the wing, where he had occasionally played under both Sir Alex Ferguson and David Moyes. He made his first start of the season in this position, assisting Juan Mata in a 1–1 draw against Sunderland on 24 August 2014.

In June 2014, Valencia was named in Ecuador’s squad for the 2014 FIFA World Cup. In a preparation match, he captained the team to a 2–2 draw with England at the Sun Life Stadium in Miami. During the match, he was fouled by Raheem Sterling and responded by shoving Sterling and grabbing him by the throat. Referee Jair Marrufo decided to send off both Valencia and Sterling. Valencia later apologized for his reaction. Valencia captained La Tri during all three of their matches at the World Cup and was sent off for a foul on Lucas Digne during their final game against France, a goalless draw at the Maracanã which saw his team eliminated.

On 25 October 2015, Valencia suffered a foot injury in a 0–0 draw with Manchester City, which required surgery and ruled him out for at least four months. He made his return on 17 March 2016 in the Europa League Round of 16 second leg against Liverpool, ending in a 1–1 draw. Valencia played the full 120 minutes at right-back in the 2016 FA Cup Final against Crystal Palace on 21 May 2016, in which United won 2–1 after extra-time.

Valencia missed the 2015 Copa América in Chile due to urgent ankle surgery. He was selected in the Ecuador squad for the 2016 Copa América Centenario and on 12 June 2016, he scored in Ecuador’s 4–0 victory over Haiti at MetLife Stadium.

Manchester United triggered a one-year extension in Valencia’s contract on 17 January 2017, keeping him at the club until 2018. On 19 March 2017, Valencia made his 200th league appearance for United and scored in injury time, after goalkeeper Víctor Valdés slipped, to complete a 3–1 victory over Middlesbrough. On 26 May 2017, two days after captaining United in the 2017 UEFA Europa League Final, his contract at the club was extended until June 2019, with an option to extend for a further year. On 17 September 2017, Valencia scored his first goal of the season in a 4–0 win against Everton with a 20-yard half-volley. Later on 14 October, Valencia captained the team in his 300th appearance as Manchester United drew 0–0 at Liverpool. After being ruled out for four weeks with a hamstring injury, Valencia returned to action as he scored the opening goal in a 3–0 home victory against Stoke City in January 2018.

At the beginning of the 2018–19 season, and after the retirement of Michael Carrick, Manchester United manager José Mourinho announced Valencia would be the club’s first captain. In March 2019, Manchester United declined to take up the option to extend Valencia’s contract by an extra year, bringing to an end his 10-year spell with the club when his contract expired in June. Valencia left Manchester United having registered 325 Premier League appearances, which remains a record for a South American player.

After being released by Manchester United, LDU Quito signed Valencia on a free transfer. He made his debut for the club in a 1–0 victory over América de Quito in the Ecuadorian Serie A on 18 July 2019.