Lacazette has featured for all of France’s national youth teams beginning with the under-16 team making his debut in the team’s 2–0 victory over Cameroon on 3 April 2007 at the Montaigu Tournament. He finished the campaign with four appearances in the tournament. With the under-17 team, Lacazette was a regular and contributed to the team’s qualification for the 2008 UEFA European Under-17 Football Championship. In the competition, he scored the game-winning goal in the team’s 2–1 win over the Republic of Ireland in the group stage. France later reached the final where the team was defeated 4–0 by Spain.

With the under-18 team, Lacazette made his debut in the team’s match against Ukraine. He featured in ten of the eleven matches the team contested scoring one goal, which came against Denmark in the Tournoi de Limoges. For under-19 duty, Lacazette was again called upon by coach Francis Smerecki, making his first appearance for the team in a 4–2 defeat against Netherlands on 9 November 2009. He scored his first goal for the team on 4 March 2010 in a 2–1 win against Ukraine. On 7 June 2010, Lacazette was named to coach Smerecki’s 18-man squad to participate in the 2010 UEFA European Under-19 Championship. In the tournament, he scored two goals in the team’s 5–0 Group A victory over Austria. France later reached the final where they faced Spain, which was essentially composed of the same players that defeated France in the 2008 UEFA European Under-17 Football Championship final. In the match, France came back from a goal down to win 2–1 with Lacazette netting the game-winning goal in the 85th minute after heading in a cross from Gaël Kakuta. France thus secured their second UEFA European Under-19 championship title.

During the second half of the 2009–10 Ligue 1 season, he was called up to the first team by manager Claude Puel and appeared on the bench in the team’s 1–0 victory over Montpellier on 2 May 2010. Three days later, Lacazette made his first team debut in a Ligue 1 home match against Auxerre. On 3 July 2010, Lacazette signed his first professional contract agreeing to a three-year deal. Due to still having another year left on his aspirant (youth) contract, the contract would start on 1 July 2011.

Lacazette’s successful campaign in the 2010 UEFA European Under-19 Championship saw the player draw interest from Italian club Roma. He also drew praise from the media, alongside international teammates Yannis Tafer and Clément Grenier, for his dedication to the club after playing in the pre-season 2010 Emirates Cup match hours after playing in the final of the 2010 UEFA European Under-19 Football Championship. Lacazette began the 2010–11 season training full-time with the first team. He scored 6 goals in 12 2010–11 CFA matches for the club’s reserve team. He scored his first competitive goal for the first team on 30 October in a Ligue 1 home match against Sochaux. His goal in the 69th minute gave Lyon a 2–1 lead, which would be the final score. Three days later, Lacazette made his European club competition debut against the Portuguese club Benfica in a 2010–11 UEFA Champions League Group B away match, appearing as a substitute in the second half with Lyon trailing 4–0. Minutes after coming onto the pitch, he assisted Lyon’s opening goal, scored by Yoann Gourcuff in the 75th minute. He also assisted Lyon’s second goal, scored by Bafétimbi Gomis in the 85th minute. Lyon, however, were unable to complete the comeback, losing 4–3. On 7 December, Lacazette scored the first European club competition goal of his career in Lyon’s final Group B match, the 88th-minute equaliser in the 2–2 home draw against Israeli club Hapoel Tel Aviv.

Due to France’s victory at the 2010 UEFA European Under-19 championship, the nation qualified for the 2011 FIFA U-20 World Cup. This resulted in Lacazette making appearances for the under-20 team. He made his under-20 team debut on 7 October 2010 in a friendly match against Portugal. The match ended 3–3 with Lacazette scoring the opening goal of the match. Three days later, Lacazette scored a double in the team’s 5–0 thrashing of the Juventus Primavera team. The match was unofficial and was contested as part of the celebration of the Treaty of Turin. On 9 February 2011, Lacazette scored the game-winning goal in a 2–1 victory over England. In March 2011, Lacazette scored goals in back-to-back matches against Peru.

On 10 June 2011, he was named to the 21-man squad to participate in the 2011 FIFA U-20 World Cup finals. He made his debut in the competition in France’s first Group A match on 30 July 2011 against the host nation Colombia (France lost the match 4–1), appearing as a substitute. In the team’s next Group A match against South Korea, Lacazette appeared as a substitute again and scored the final goal (in second-half injury time) of the match, which France won 3–1. He scored one goal in France’s final Group A match, 2–0 win over Mali. Lacazette scored twice in the quarterfinal win over Nigeria and one goal in the third place match against Mexico. He finished as the tournament’s joint top scorer with 5 goals, along with Henrique Almeida and Álvaro Vázquez.

On 23 May 2013, Lacazette received his first call-up to the senior squad following the withdrawal of Jérémy Ménez through injury. He made his international debut on 5 June, as a 58th-minute substitute for Olivier Giroud in a 0–1 friendly defeat against Uruguay at the Estadio Centenario in Montevideo. Lacazette scored his first international goal on 29 March 2015, opening a 2–0 friendly win over Denmark at the Stade Geoffroy-Guichard in Saint-Étienne. During the match, he was booed by some of the local supporters due to their rivalry with Lyon. On 14 November 2017, Lacazette netted a brace for France during a friendly away to Germany in an eventual 2–2 draw.

Lacazette scored Lyon’s only goal in the 2014 Coupe de la Ligue Final against Paris Saint-Germain; however his side lost 2–1.

In September 2014, Lacazette signed a two-year extension to his contract, tying him to the club until 2018. He scored his first hat-trick on 5 October 2014, scoring all the goals in a 3–0 Ligue 1 home win over Lille. On 26 April 2015, Lacazette broke the Lyon record for Ligue 1 or Division 1 goals scored in a single season with his 26th in a Ligue 1 4–2 away victory over Reims; André Guy had scored a total of 25 Division 1 goals in the 1968–69 season. He finished the 2014–15 Ligue 1 season as the top scorer in Ligue 1, scoring a total of 27 goals. Lacazette completed an outstanding season by being voted Ligue 1 Player of the Year for the 2014–15 season.

Amid transfer speculation from a number of Premier League clubs such as Arsenal following his break-out season, on 8 August 2015, Lacazette signed a new deal, extending his contract with Lyon until 2019. On 8 November 2015, he scored all of the goals in a 3–0 Ligue 1 home win over local arch-rivals Saint-Étienne. On 9 January 2016, he scored the first goal at the newly opened Parc Olympique Lyonnais, in a 4–1 win over Troyes in a Ligue 1 match.

On 29 October 2016, Lacazette scored two goals in Lyon’s 2–1 away win against Toulouse in Ligue 1 to register his 100th and 101st goals in all competitions for Lyon, overtaking Juninho Pernambucano (who scored 100 goals in 350 competitive matches for Lyon) to become the fourth-most prolific scorer in Lyon’s history. On 22 November, he scored the only goal by slotting home Rafael’s rolled cross from close range in the 72nd minute of the 2016–17 UEFA Champions League group stage Group H matchday 5 1–0 away win against Dinamo Zagreb to keep alive Lyon’s hopes of progressing to the knockout phase of the 2016–17 UEFA Champions League.

In May 2017, it was reported that a verbal arrangement had been reached for Lacazette to join Atlético Madrid in the summer of 2017, but that fell through on 1 June 2017, after the Court of Arbitration for Sport upheld Atlético’s ban on registering players for two transfer windows (1 January – 2 February 2017 and 1 June – 31 August 2017) that was imposed in July 2016 by FIFA on the club for breaching FIFA rules over the signing of minors. Lacazette was given the number 9 jersey.

On 5 July 2017, Lacazette signed a reported five-year deal for Premier League club Arsenal for a club record fee; Lyon disclosed that the fee was an initial €53 million (£46.5 million) plus up to €7 million (£6.1 million) in potential bonuses. The fee was the largest ever received by Lyon from the sale of a player, beating the €41.5 million (£37.7 million) record set by Corentin Tolisso’s transfer to Bayern Munich three weeks earlier. The transfer fee also surpassed the previous Arsenal record €50 million (£42.5 million) that Arsenal paid Real Madrid for Mesut Özil in 2013.

On 6 August 2017, Lacazette made his first appearance for Arsenal in the 2017 FA Community Shield against Chelsea. Despite hitting the post midway through the first half, Arsenal eventually won 4–1 on penalties after the game ended 1–1 at full time. This win constituted his first trophy win at Arsenal. On 11 August, Lacazette made his Premier League debut against Leicester City and scored after 94 seconds to give Arsenal a 1–0 lead in an eventual 4–3 win. Lacazette also managed to score in both of Arsenal’s next home games, scoring Arsenal’s second in a 3–0 win over Bournemouth, before grabbing a brace for the club in a 2–0 win over West Bromwich Albion. With his goals against West Brom, Lacazette became the first Arsenal player to score in his first three home league appearances for the club since Brian Marwood in September 1988.

Lacazette previously played as a winger for Lyon, before becoming a striker. As well as goalscoring and finishing ability, characteristics of his game are pace, strength, balance, technique, dribbling, link-up play, and ability with either foot. He is also a hard-working player, who presses the opposition and wins the ball back using his defensive skills and tackling ability. Fellow Frenchman Gérard Houllier said in July 2017 that Lacazette “is a bit like” former Arsenal striker Ian Wright.

On 17 May 2018, he was named on the standby list for the 23-man French squad for the 2018 World Cup in Russia.

After the departure of manager Arsène Wenger, Lacazette found himself dropped to the bench under new manager Unai Emery, making substitute appearances against Manchester City, Chelsea and West Ham United. Lacazette made his first start under Emery in Arsenal’s 3–2 away win over Cardiff City on 2 September, where he registered an assist and scored his first goal of the season. On 1 April 2019, Lacazette scored Arsenal’s second goal in a 2–0 win over Newcastle United, which sent Arsenal into third place and two points clear of rivals Tottenham Hotspur, Chelsea and Manchester United. The goal marked Lacazette’s thirteenth goal of the season in the Premier League. On 3 May 2019, Lacazette was voted by Arsenal supporters as the club’s player of the season.

Lacazette scored his first goal of the 2019–20 season in Arsenal’s home opener, a 2–1 victory against Burnley on 17 August 2019. On 1 August 2020, Lacazette was selected to start in the FA Cup Final against Chelsea, as Arsenal won their 14th FA Cup.

Lacazette scored Arsenal’s first league goal and first Premier League goal of the 2020/21 season in a 3–0 victory against Fulham on 12 September 2020.