Inzaghi’s favourite footballers as a child were Paolo Rossi and Marco van Basten. The elder brother of fellow footballer Simone Inzaghi, he got his start playing for hometown club Piacenza as a teenager in 1991, but made only two league appearances before being loaned to Serie C1 side AlbinoLeffe, with whom he scored an impressive 13 goals in 21 matches. In 1993, Inzaghi moved to Serie B club Hellas Verona and scored 13 goals in 36 league appearances. Upon his return to Piacenza, he scored 15 times in 37 games helping his team win Serie B and proving himself to be an exciting young prospect.

Between 1993 and 1996, Inzaghi made 14 appearances for the Italy under-21 team, scoring three goals; he was also a member of the Italy under-21 squad that won the 1994 UEFA European Under-21 Football Championship. Inzaghi earned his first senior cap for Italy in the Tournoi de France, against Brazil on 8 June 1997, under his former under-21 manager Cesare Maldini, and provided an assist to goalscorer Alessandro Del Piero. Italy went on to draw 3–3. He scored his first goal for Italy on 18 November 1998, in a 2–2 friendly draw against Spain; he has since scored 25 goals in 57 appearances. He was called up for the 1998 FIFA World Cup, Euro 2000, the 2002 World Cup and the 2006 World Cup.

Inzaghi made his Serie A debut when he transferred to Parma in 1995, but scored only twice in 15 league matches. One of these two goals came against one of his former clubs, Piacenza, literally “making him cry”. He added another two goals in European competitions that season. The following season, he moved on to Atalanta, finishing as the Capocannoniere (Serie A’s top scorer) with 24 goals, and scored against every team in the league. He was awarded Serie A Young Footballer of the Year and served as team captain in the last game of the season.

During his first season with the club, Inzaghi scored two goals as Juventus beat Vicenza 3–0 in the 1997 Supercoppa Italiana. Juventus won the Scudetto during the 1997–98 season, in which Inzaghi scored 18 goals, including a decisive, Scudetto-winning hat-trick against Bologna. He also scored six goals to help Juventus reach the Champions League final, although they were defeated 1–0 by Real Madrid.

The 1998–99 season was less successful for Juventus, as they suffered a defeat in the 1998 Supercoppa Italiana to Lazio, and finished the season with a disappointing seventh place in Serie A. Inzaghi still managed 20 goals in all competitions, finishing the season as the club’s top-scorer; Six of his goals came in the Champions League, as Juventus were eliminated in the semi-finals by eventual champions Manchester United. During the second leg of the semi-finals in Turin, Inzaghi scored two goals in the first ten minutes, but Manchester United eventually managed to come back and win the match 3–2.

With 70 goals, Inzaghi is the fifth-highest scorer in European club competitions, behind only Raúl, Cristiano Ronaldo, Lionel Messi and Robert Lewandowski. He became the first player to score two Champions League hat-tricks – both with Juventus — when he netted a treble during a 4–4 group stage draw with Hamburger SV on 13 September 2000; his first was in a 4–1 victory over Dynamo Kyiv during the 1997–98 quarter–finals. Inzaghi scored a record third Champions League hat-trick in a 4–0 win against Deportivo de La Coruña in the 2002–03 season, while playing for Milan. This record would later be tied by Michael Owen, who has scored two hat-tricks for Liverpool and a third for Manchester United.

Despite a very good tally of 89 goals in 165 games for the Bianconeri, Inzaghi was soon benched in favour of David Trezeguet and on 2 July 2001 signed for Milan for a reported 70 billion lire, or 45 billion lire cash plus Cristian Zenoni. (Sky Sports reported a smaller total figure, £17 million) for the 2001–02 campaign by coach Fatih Terim. Juventus announced that the sale of Inzaghi produced a capital gain of €31.1 million to the club, making the actual transfer fee much exceed that figure. Inzaghi, however, suffered a knee injury and missed the first half of the season. Upon his return, he was able to forge a strong goalscoring partnership with Andriy Shevchenko, and he soon racked up an impressive trophy count with the Rossoneri under new manager Carlo Ancelotti, among them the 2002–03 Champions League (in which Milan defeated his previous team, Juventus, in the final on penalties), along with the 2002–03 Coppa Italia (scoring in a 2–2 draw in the second leg), the 2003 UEFA Super Cup, the 2004 Supercoppa Italiana, and the 2003–04 Scudetto. In the 2002–03 Champions League campaign, he scored his record third Champions League hat-trick against Deportivo de La Coruña in the Group Stage and a decisive goal in quarter-finals against Ajax, totalling 12 European goals in that season. In November 2004, he signed a contract extension with the club.

At the start of the 2007–08 season, he picked up where he left off in Athens, scoring the equalizer in the Super Cup in Milan’s 3–1 victory over Sevilla. Inzaghi capped off the year by scoring two goals in the final of the 2007 Club World Cup, helping Milan win 4–2 against Boca Juniors to take revenge for the defeat on penalties in 2003.

Under Zoff’s replacement, Giovanni Trapattoni, Inzaghi was Italy’s top goalscorer during the qualifying rounds of the 2002 World Cup and Euro 2004, scoring his first and only international hat-trick in a 4–0 home win over Wales on 6 September 2003, although he missed the latter tournament due to injury. He went scoreless throughout the 2002 World Cup, making two appearances, as Italy were controversially eliminated in the round of 16 to co-hosts South Korea; in Italy’s 2–1 loss to Croatia in their second group match, Materazzi played a floating ball over the top from just over half way to Inzaghi in the 90th minute, but everyone missed the ball and it rolled into the back of the net, although the goal was disallowed after referee Graham Poll claimed that Inzaghi had grabbed an opponent’s shirt. Inzaghi also had a goal wrongly disallowed in Italy’s final group match against Mexico, which ended in a 1–1 draw.

Inzaghi’s persistent knee and ankle injuries put a halt to his international play for almost two years before his resurgence at club level, which resulted in being called up by Italy coach Marcello Lippi for the 2006 World Cup final tournament. Due to the abundance of other top strikers such as Alessandro Del Piero, Francesco Totti and Luca Toni, Inzaghi made his only appearance – subbing on for Alberto Gilardino — in Italy’s final group stage match against the Czech Republic on 22 June 2006, scoring his only goal in the tournament, rounding Petr Čech in a one-on-one encounter to net in Italy’s second goal, which made him the oldest player to have scored for Italy in a World Cup, after Daniele Massaro. Italy went on to win the tournament, defeating France on penalties in the final.

Inzaghi was able to fully recover from persistent knee injuries that had dogged him for two years to the extent that he regained his predatory goalscoring form by scoring 12 goals in 22 Serie A matches in 2005–06, along with four goals in five Champions’ League appearances; two against Olympique Lyonnais in the quarter-finals and another two against Bayern Munich in the first knockout stage. He scored the decisive goal against the Bavarians in the 2007 quarter-finals, helping Milan to reach the semi-finals of the competition. On 23 May 2007, in the 2007 Champions League final in Athens, he scored both of Milan’s goals in their 2–1 victory over Liverpool in a rematch of the 2005 final. He declared after the match:

Following Italy’s fourth World Cup victory, Inzaghi made six appearances under new manager Roberto Donadoni in Italy’s UEFA Euro 2008 qualification campaign, scoring three goals, two of which came in a 2–1 away win against the Faroe Islands on 2 June 2007. He was not called up for the final tournament, however, where Italy were eliminated by eventual champions Spain in the quarter-finals on penalties, and he made his last appearance for Italy on 8 September 2007, in a 0–0 draw against France in Milan.

On 24 February 2008, Inzaghi scored the match-winning goal in Milan’s 2–1 win over Palermo with a diving header after coming into the game from the bench; it marked his first Serie A goal in over a year. This was followed by ten more goals in the league, the last against Udinese. This strike against Udinese was his 100th goal for the club in official games. But despite incredible form, Italy national team manager Roberto Donadoni declined to call him for Euro 2008. In November 2008, Inzaghi agreed to a contract extension with Milan until June 2010.

On 8 March 2009, Inzaghi scored his first hat-trick of the season for Milan against Atalanta, leading his team to a 3–0 victory at the San Siro. His 300th career goal came in the 5–1 thrashing of Siena away from home. He then went on to score three goals against Torino, his second professional hat-trick in that season. Scoring this hat-trick enabled “Super Pippo” — his nickname in the media – to set a record for the player with the most hat-tricks in Serie A over the last 25 years. With ten hat-tricks in Serie A, Inzaghi is ahead of Giuseppe Signori (9), Hernán Crespo (8), Roberto Baggio, Marco van Basten, Gabriel Batistuta, Abel Balbo, Vincenzo Montella (7), Antonio Di Natale and David Trezeguet (6). Inzaghi scored one hat-trick for Atalanta, four for Juventus, and five for Milan.

In the 2009–10 season, under manager Leonardo, Inzaghi was relegated to the role of backup player with his contract set to expire in June 2010. On 21 May 2010, he was offered a new one-year contract which would last until 30 June 2011.

On 3 November 2010, in the UEFA Champions League 2010–11 Group Stage campaign, with Milan trailing by 1–0 to Real Madrid, Inzaghi came off the bench in the second half and scored a brace to give Milan a 2–1 lead. Pedro León, however, equalized in the 94th minute, with the final score ending 2–2. On that occasion, he became the new all-time top scorer of all European club competitions with 70 goals. He also became the second-oldest player to score in the Champions League, aged 37 years and 85 days, behind only Manchester United’s Ryan Giggs, now surpassed by Inzaghi’s compatriot Francesco Totti. With these two goals, Inzaghi went ahead of his idol Marco van Basten on the club list of the all-time top goalscorers with 125 goals.

On 10 November 2010, Inzaghi suffered a serious injury while playing for Milan against Palermo. A statement on the official Milan club website confirmed that Inzaghi had suffered a lesion of the anterior cruciate ligament (ACL) and associated lesion to the external meniscus of the left knee. It was thought he would be out for the rest of the season. Due to his age, this injury could have ended his career; nonetheless, Inzaghi was very optimistic. On 7 May 2011, with Inzaghi still out recovering from his injury, Milan won the 2010–11 Serie A title. After being sidelined by injury for six months, he came off the bench for the first time since his injury on 14 May, with Milan defeating Cagliari 4–1. He extended his contract till June 2012 during the 2011–12 pre-season.

Just like with Andrea Pirlo in 2011, Milan decided not to renew the contracts of several veteran players at the end of the season and Inzaghi was one of those, along with Gennaro Gattuso, Clarence Seedorf, Alessandro Nesta, and Gianluca Zambrotta. He played his final game for Milan against Novara on 13 May 2012 and marked his performance by scoring the winning goal, much to the joy of the fans. On 24 July 2012, Inzaghi announced his retirement from professional football to start a coaching career.

On 9 June 2014, Inzaghi was named manager of Milan’s first team after the dismissal of his former Rossoneri teammate Clarence Seedorf. In Inzaghi’s first match as a manager in Serie A on 31 August, Milan defeated Lazio 3–1 at the San Siro. Inzaghi then led Milan to a second consecutive win in an exciting match that ended with a 5–4 Milan win against Parma.

On 4 June 2015 Adriano Galliani, the CEO of Milan, announced that Inzaghi would not be the coach for next season. He was officially dismissed on 16 June 2015.

In 2015, the arcade game company Konami announced that Inzaghi would feature in their football video game Pro Evolution Soccer 2016 as one of the new myClub Legends.

On 7 June 2016, Inzaghi was appointed as the new coach of ambitious Lega Pro club Venezia. On 19 April 2017, after beating Parma to top spot, he won promotion to Serie B as champions. He also won the Coppa Italia Lega Pro in the same season.

On 13 June 2018, Inzaghi was announced as the new head coach of top-flight Bologna, taking over from Roberto Donadoni. He faced a Lazio side coached by his younger brother Simone in an eventual 0–2 defeat on 26 December. Following a record of two wins in 21 games, he was dismissed on 28 January 2019 and replaced by Siniša Mihajlović.

On 22 June 2019, Inzaghi was appointed manager of Benevento in Serie B. On 30 June the following year, his club achieved promotion as champions with seven games remaining, reaching Serie A for the second time in their history. He successfully debuted with a 3-2 away against Sampdoria, after the home team was leading 2-0.