Trezeguet began his career in Argentina with Club Atlético Platense at the age of eight, progressing through their youth system to their first team, where he made his debut in the Primera División in 1994.

[9] Trezeguet began his career at Platense in the Argentine Primera División, where he played his first professional game on 12 June 1994 as a 16-year-old in a 1–1 tie against Gimnasia.

[10] Monaco coach Jean Tigana was "impressed" by Trezeguet, who scored five goals in trial, signing a deal which saw him earn 15,000 francs a month.

[12] In 1998, Trezeguet scored the fastest ever goal in terms of velocity in UEFA Champions League history in a quarter-final match against Manchester United.

In January 2002, a car carrying Trezeguet and teammates Mark Iuliano, Gianluca Zambrotta and Enzo Maresca after a 3–1 win over Hellas Verona, collided with two others; none of the four players were injured in the accident.

During the 2003–04 season, Trezeguet helped the team to win a second consecutive Supercoppa Italiana title, scoring a goal during the match, also reaching another Coppa Italia final, although their European and domestic league campaigns would be less successful, despite his 16 goals in Serie A that season, as the club finished the league in third place.

Following the enforced relegation to Serie B, the club lost several of its star players, including Fabio Cannavaro to Real Madrid, Gianluca Zambrotta to Barcelona, Adrian Mutu to Fiorentina, and Zlatan Ibrahimović to Internazionale.

After scoring a goal in Juventus' final match of the 2006–07 Serie B season against Spezia, Trezeguet made a gesture toward the club president, making a number 15 with his fingers – the number of goals he scored throughout the Serie B season – which was followed by a hand gesture which, in Italian, means "I'm out of here".

[15][16] During the 2007–08 Serie A season, Trezeguet scored 20 league goals and was second only to teammate and club captain Alessandro Del Piero for the Capocannoniere.

Trezeguet would shortly get his first goal of 2009 in a 2–0 win against Palermo in late February – a match where he received the captaincy for the first time in his professional career.

[18] On 28 August 2010, Trezeguet completed his move to newly promoted La Liga team Hércules on a two-year deal; the club is based in his then wife's hometown.

[citation needed] On 30 August 2011, Trezeguet completed his move to UAE Pro-League side Baniyas on a one-year deal.

[25] On 19 December 2011, Trezeguet moved to River Plate in Argentina on a three-year contract, shortly after the club was relegated to the Argentine second division for the first time in its history.

He played his first match at Estadio Monumental the following week and scored his first official goal for River Plate after coming on as a substitute.

[citation needed] Trezeguet would later state that the adrenaline he gets while playing for River surpasses any other moment he experienced in his career, including winning the 1998 FIFA World Cup with France and scoring the golden goal in the finals of UEFA Euro 2000: "I am feeling things that I have never felt before.

In the 83rd minute he scored the second goal of the game with his side winning 2–0 against Racing Club, a team which Trezeguet's former Juventus teammate Mauro Camoranesi played for and was subbed on earlier in the match.

In the lead up to the 1998 World Cup in France, Aimé Jacquet gave younger players such as David Trezeguet, Henry and Patrick Vieira the chance to display their talent, and all three were eventually selected for the World Cup ahead of experienced French players including David Ginola.

Two years later France were crowned European champions after defeating Italy 2–1 in the Euro 2000 final, courtesy of Trezeguet's golden goal in extra time from a Robert Pires assist.

The failure was then followed up by a quarter-final exit at Euro 2004 at the hands of unheralded Greece with Trezeguet scoring just one goal in the tournament in a 2–2 draw against Croatia.

Throughout the tournament, Trezeguet found himself out of place in Raymond Domenech's 4–2–3–1 formation which only used one striker – a position allocated to Thierry Henry.

[13] On 19 October 2007, Trezeguet threatened to quit France after being overlooked for two Euro 2008 qualifying matches by coach Raymond Domenech.

[40] On 26 March 2008, Trezeguet was selected for a friendly against England to replace the injured Karim Benzema, which would turn out to be his last appearance for France as he was subsequently not chosen for the squad that competed in Euro 2008.

[42] He cited "the awful Euro 2008 and the reappointment of the coach" being the main reasons for this decision, and also added "I see football differently from how they see it in France.

[13][44] A highly opportunistic player, he was excellent at taking advantage of chances and loose balls in the area, and was an accurate striker of the ball, known for his clinical finishing, as well as his ability to score with few touches, due to his ability to shoot first time and finish off chances from close range, even when off-balance or from awkward positions.