David Luiz made his debut for Vitória in 2006, excelling in a 2–2 draw against Santa Cruz in that season’s Copa do Brasil. At the worst situation of its history, in the third division, the club eventually promoted to the second level after finishing in second position, with the player appearing in eight of the club’s last decisive nine games, scoring his only league goal on 3 September 2006 in a 2–0 home win against Clube Atlético do Porto.

On 30 January 2007, David Luiz joined Portuguese club Benfica as a replacement for Tottenham Hotspur-bound Ricardo Rocha, on loan. He made a somewhat tumultuous debut for the club in a UEFA Cup match against Paris Saint-Germain at the Parc des Princes, partnering compatriot Anderson in the centre of defence, replacing the injured Luisão. Benfica lost the match 2–1 but progressed to the next round after winning 4–3 on aggregate.

On 12 March 2007, David Luiz played his first league match for Benfica, against União de Leiria. At the end of the season, following ten league appearances, he joined permanently for a €1.5 million transfer fee and signed a five-year contract with the club. Before the ensuing campaign, he scored his first goal for the club in the Guadiana Trophy friendly tournament, against Sporting CP. However, David Luiz only managed eight appearances in the league due to injury as Benfica finished fourth.

David Luiz played with the Brazil under-20 team at the FIFA U-20 World Cup in 2007, with the team being ousted in the round of 16.

On 11 January 2009, David Luiz scored his first goal for Benfica, the match’s only goal in a home success against Braga. He played most of the campaign as a left back, at the expense of Portuguese international Jorge Ribeiro.

On 30 September 2009, Benfica sold 25% of David Luiz’s economic rights on any future transfer to a third-party owner, Benfica Stars Fund, along with other teammates. He was valued at €18 million, with the fund paying €4.5 million; his contract was also renewed in October with a release clause of €50 million.

Courtesy of his solid season at Benfica, he was first picked for the senior side in a 2–0 friendly win against the United States on 10 August 2010, the first match after Mano Menezes replaced Dunga as the coach of the Seleção. Prior to making his debut for Brazil, the Portuguese Football Federation had considered calling him up to their own national team.

On 31 January 2011, David Luiz completed a move to Chelsea for a €25 million transfer fee and subsequently signed a five-and-a-half-year contract. As part of the deal, Chelsea midfielder Nemanja Matić joined Benfica at the end of the season after his transfer spell at Dutch club Vitesse.

David Luiz was present in every squad during the management of Menezes and was called up to the squad for the Copa América in 2011, but did not make a single appearance at the tournament due to injury. In a friendly with Mexico in October of that year, he scored an own goal, but the Seleção eventually won it 2–1.

Although primarily a centre back, David Luiz can also be deployed as a defensive midfielder or as a full back, and has drawn praise for his physical strength, work-rate, technique, and range of distribution as a defender, as well as his personality, composure in possession, and confidence on the ball, which enables him to play the ball out from the back or launch an attack with long balls after winning back possession. A powerful striker of the ball from distance, Luiz has also been known to take and score from long-range free kicks, which led Tim Vickery to liken him to compatriot Lúcio in 2011. Although in the past he has been criticised in the media for his inconsistent defensive performances, and for being reckless in his challenges, as well as prone to errors or lapses in concentration, during the 2016–17 season, he showed notable improvements upon his return to Chelsea, when the club’s new manager Antonio Conte decided to deploy him as a ball-playing centre back in a three-man back-line in the team’s 3–4–3 formation. Luiz excelled in the new role, while Conte praised the defender for working to improve his composure and concentration, and singled out Luiz as being “crucial” to the team’s success, also labelling him as one of the best defenders in the world.

On 5 February 2012, in a league home fixture against Manchester United, David Luiz put Chelsea ahead 3–0 in the 50th minute after his header was deflected by Rio Ferdinand, following a Juan Mata free kick. The match ended with a 3–3 draw. On 25 February, through a curled shot, he opened the score against Bolton Wanderers in an eventual 3–0 at home.

On 22 September 2012, David Luiz signed a new five-year contract with Chelsea. He started the new season again as a regular alongside either Gary Cahill or Terry, and scored his first goal from a free-kick against Nordsjælland in a 0–4 away win in the campaign’s Champions League. In the Club World Cup in 2012, in which Chelsea lost in the final to Corinthians, he was chosen the second best player of the tournament, receiving the Silver Ball for his performances, one of which was as a defensive midfielder. He played in that position in an 8–0 home thrashing of Aston Villa the following week, being chosen man of the Match and netting the second from a free-kick.

On 7 September 2012, David Luiz captained Brazil for the first time, appearing in a 1–0 win against South Africa in São Paulo. He was included in the squad for the FIFA Confederations Cup in 2013, which was hosted in his native Brazil. Alongside teammate Thiago Silva, David Luiz started all matches and helped Brazil win their fourth Confederations Cup title. In the final against Spain, he made an outstanding goal-line clearance from Pedro’s shot.

On 17 April 2013, David Luiz scored during a 3–0 West London derby victory against Fulham. He also scored in both legs of the Europa League semi-finals against Basel; the first was a last minute, low free-kick curled around the wall and into the goalkeeper’s bottom left-hand corner to secure a dramatic 2–1 away win, giving Chelsea an advantage going into the second leg at Stamford Bridge.

On 13 June 2014, David Luiz transferred to French club Paris Saint-Germain for a £50 million transfer fee, a world-record transfer for a defender, signing a five-year contract.

On 19 January 2015, David Luiz scored his first Ligue 1 goal in a 4–2 defeat of Evian. On 11 March, he scored on his return to Stamford Bridge in the round of 16 of the Champions League as PSG drew 2–2 with his former club Chelsea to knock out the English club on away goals. He apologised for celebrating the goal, saying that it was the result of sudden emotion rather than malice towards his former employers.

On 13 November 2015, David Luiz received his first career red card in a 1–1 2018 World Cup qualifying draw with rivals Argentina in Buenos Aires. In 2016, David Luiz and Thiago Silva were among several experienced players who were not chosen for the squad that travelled to the Copa América Centenario in the United States.

David Luiz is a devout Evangelical Christian and has named Kaká as his role model. He said, “My faith gives me the belief that I can go out and perform and improve as a player. It gives me strength and inspiration.” He later added, “Everything in life belongs to God. Our purpose has already been mapped out.” He received baptism in May 2015 in the indoor swimming pool of his Brazil and PSG teammate Maxwell.

David Luiz returned to Chelsea from PSG, for a reported fee of £34 million, in August 2016 and signed a three-year deal. His first game back with the club was a 2–1 defeat at home to Liverpool on 16 September. On 31 January 2017 he scored his first goal for the season from a free kick against Liverpool at Anfield, his first Premier League goal since April 2013. At the end of the season, David Luiz was named in the PFA Team of the Year for 2016–17.

David Luiz was selected for Chelsea’s first match of the 2017–18 Premier League season, against Burnley on 12 August 2017, and scored late on in their 3–2 defeat. On 17 September 2017, Luiz received a straight red after a poor challenge on Sead Kolašinac during a 0–0 draw against Arsenal. Luiz became the third player to be sent-off in the last three meetings between the two rivals from London; with the others being Pedro during the FA Community Shield and Victor Moses during the FA Cup Final.

In 2018, Luiz and his teammate Willian acquired Babbo, an Italian restaurant located in Mayfair, London.

David Luiz scored his first goal of the 2018–19 Premier League, heading in the second goal in Chelsea’s 2–0 home win over the previously undefeated Manchester City on 8 December. He hit the winning penalty in a 4–2 shootout win in the EFL Cup semi-final second leg at home to Tottenham Hotspur on 24 January 2019.

On 8 August 2019, Arsenal signed David Luiz from Chelsea for a reported £8 million transfer fee. He received the number 23 shirt for the club. On 6 October 2019, he scored the match’s winning goal, his first for Arsenal, in a 1–0 victory against AFC Bournemouth. In a 2–2 home draw against Crystal Palace, he scored his second Arsenal goal. In a match against former club Chelsea in January 2020, he was sent-off after conceding a penalty. While Arsenal eventually drew the match, David Luiz received a three-match suspension from domestic play. He made his return in a Premier League match against Everton, during which he recorded his first assist for Arsenal.

In Arsenal’s final match of the season, David Luiz gave away a penalty against Watford; this was the fifth penalty he had conceded that season, setting a Premier League record for most penalties conceded by a single player in a single season. On 1 August 2020, David Luiz was selected to start in the FA Cup Final against his former club Chelsea, as Arsenal won their 14th FA Cup.

On 29 August 2020, David Luiz started the game and scored the fourth penalty in a shootout win against Liverpool in the 2020 FA Community Shield after the game ended 1–1.