Born in La Plata, Palermo began his career at Estudiantes de La Plata and later transferred to Boca Juniors. His good goal average and performances in international matches led European teams Lazio, Real Betis and Milan to be interested in signing him up. But on 13 November 1999, in a game against Colón, he had a complete tear of the anterior cruciate ligament of his right knee; before leaving and without knowing the seriousness of the injury, he scored his 100th goal in the Argentine First Division.
He took six months to recover from the injury. On 24 May 2000, he returned, playing the last fifteen minutes of the quarterfinal match of the Copa Libertadores against River Plate and scoring a goal, leaving the score at 3–0 to Boca Juniors (the first match had ended 1–2).
With Boca he scored many goals, particularly against arch-rivals River Plate.
He played in the Intercontinental Cup in 2000, scoring the two goals in Boca's 2–1 victory over Real Madrid, winning the man of the match award and catching the attention of football clubs in Spain.
Palermo signed with the up-and-coming team Villarreal of the Spanish La Liga on 19 January 2001 in a €7,600,000 transfer. In his second season with the team on 29 November, after scoring a goal, Palermo stood on a small concrete wall, which collapsed under the weight of Villarreal's fans and broke both the tibia and fibula of his left leg, leading to two months of inactivity. Palermo never regained his form, and after two and half seasons with Villarreal, on 20 August 2003, he left the club. The following day Palermo signed a contract with Real Betis, but in March 2004, after very little success with the club, he left. Later that month he signed with Alavés of the Spanish second division.
On 13 July 2004, after three and a half years of playing in Spain for Villarreal, Real Betis, and Alavés, Palermo returned to Boca Juniors. On 17 December he scored his 100th goal with Boca on the final of the 2004 Copa Sudamericana a 2–0 victory over Bolívar.
Palermo, once again back in top form, remained one of the best scorers in the Argentine league, scoring 11 goals in three consecutive matches (2006 Clausura, 2006 Apertura and top scorer of the 2007 Clausura). During the 2007 Clausura tournament he had several memorable moments, the first of which came on 25 February, when he scored a half pitch goal in the last seconds of a 3–1 victory over Independiente, two of weeks later, on 10 March, he scored three goals against his former team Estudiantes in a 3–1 Boca victory at La Plata. It was the fourth hat-trick of his career. A game later, on 18 March, he scored a career high of four goals in the 5–1 victory against Gimnasia de la Plata, Estudiantes de La Plata's archi-rivals.
The following season the 2007 Apertura, he continued to be among the Argentine league top scorers with 13 goals. His best game that season was on 16 September, in a game against Banfield, in which he scored four goals, in the 6–0 Boca victory.
Palermo scored his fifth career hat-trick in a 3–0 Boca Juniors victory, a must-win game played in Jalisco, Mexico, against Atlas on 21 May 2008.
At the beginning of the 2008 Apertura, on 24 August he suffered yet another serious injury, this time he injured his anterior cruciate and tore his medial collateral ligament during the 2–1 victory against Lanús, with an expected recovery period of 5 to 8 months. After this was known, Argentine coach Alfio Basile said that he had chosen him to play for the national team for the following match in the World Cup qualifiers
Palermo's first goal since his injury came on the fourth game he played, during a 3–1 victory over Huracán on 1 March in the 2009 Clausura; this was Martín Palermo's 195 goal with Boca Juniors, breaking Francisco Varallo record of 194 goals in the professional era. Nearly two months later. on 30 April, Martín scored a bicycle kick goal, which gave him 200 goals with Boca Juniors, in a 3–0 victory against Deportivo Táchira.
During the 2009 Apertura, on 4 October in a game against Vélez Sársfield, Martín Palermo scored a very special goal (a header that traveled around 38.9 meters), this goal gave him 200 goals in the Argentine First Division and also gave Boca a 3–2 victory.
On 22 July 2010, at 36 years of age, Palermo announced that he had renewed his contract with Boca Juniors for one year and that he will retire at the end of the contract.
Martín Palermo scored his sixth career hat-trick on 19 September 2010 in a 3–1 Boca victory over Colón.
On 13 December 2010, Palermo scored his 300th career goal in the final match of the 2010 Apertura in a 1–1 draw against Gimnasia de La Plata.
On 24 April 2011, Martin scored the third goal of Boca Juniors against Huracán in a 3–0 away win, with that goal Palermo cut a streak of 10 matches without scoring. Then he scored in the next consecutive matches against Independiente, Argentinos Juniors and in the 2–0 victory over River Plate in the Superclasico.
Palermo achieved legendary status in Boca in the last few years, thanks to his many memorable goals for both the club and the Argentina national team. On 12 June 2011, Palermo played his last home match at La Bombonera, after the match Martín was honored by Boca Juniors and was given several gifts, among the gifts was one of the goal frames of the stadium.
Palermo officially retired from football on 18 June 2011, in a 2–2 draw against his classic rival Gimnasia de La Plata. He provided a headed assistance for Boca's second goal in the last minute of the match, marking the end of a 19-year playing career at senior level.
With the Argentina national football team, Palermo has played fifteen matches and scored nine goals. He is in the Guinness Book of World Records for missing three penalties for Argentina in a single international match against Colombia in the 1999 Copa América. The first penalty rebounded off the crossbar; the second penalty went over; the third was saved by the Colombian goalkeeper, Miguel Calero. Though his international career seemed to be over at the end of 1999, the 2008 Argentine national coach Alfio Basile stated that he had been considering offering Palermo a return to international football and was disappointed that Palermo was injured at the time.
The coach of the 2010 national team, Diego Maradona, recalled Palermo to the national team and introduced him as a substitute in a 2010 World Cup qualifying match against Paraguay after a 10-year exile from the international scene. A couple of weeks later he was once again called up to play a friendly against Ghana. In this game, Palermo was part of the starting eleven and made the most of it by scoring both of Argentina's goals, resulting in a 2–0 win. Palermo's next match was on 10 October, a 2010 World Cup qualifier against Peru. Palermo sealed a 2–1 victory for Argentina with a 93rd-minute strike, causing Maradona to describe the goal after the game as "one more miracle of Saint Palermo."
On 19 May 2010, Palermo was selected as part of the Argentina national team's 23-man final roster for the 2010 FIFA World Cup in South Africa, Palermo's first World Cup. On 22 June 2010, Palermo played his first World Cup match, coming in as a substitute in the second half of Argentina's final group match against Greece. In the 89th minute, he scored his first ever World Cup goal on a rebound from a shot by Lionel Messi. Argentina won the match 2–0 and finished at the top of their group. This goal also made Palermo the oldest Argentine national footballer to score a goal in World Cup play, an honor previously held by Diego Maradona.Estudiantes
Primera B Nacional (1): 1994–95
Primera División (6): 1998 Apertura, 1999 Clausura, 2000 Apertura, 2005 Apertura, 2006 Clausura, 2008 Apertura
Copa Libertadores (2): 2000, 2007
Intercontinental Cup (1): 2000
Copa Sudamericana (2): 2004, 2005
Recopa Sudamericana (2): 2006, 2008
Primera División top scorer (2): 1998 Apertura (20 goals, short tournament record), 2007 Clausura
Boca Juniors top scorer (16): 1998 Clausura, 1998 Apertura, 1999 Clausura, 1999 Apertura, 2000 Apertura, 2004 Apertura, 2005 Clausura, 2006 Clausura, 2007 Clausura, 2007 Apertura, 2008 Clausura, 2009 Clausura, 2009 Apertura, 2010 Clausura, 2010 Apertura, 2011 Clausura
South American Footballer of the Year (1): 1998
South American Team of the Year (2): 1998, 2000
Intercontinental Cup Man of the match (1): 2000
American Golden Shoe (1): 2007 (shared with Giancarlo Maldonado)
First professional match: 5 July 1992 Clausura. (San Lorenzo 0–0 Estudiantes)
First professional goal: 22 May 1993 Clausura. (Estudiantes 3–0 San Martín de Tucumán)
First International match: 3 February 1999. (Venezuela 0–2 Argentina)
First International goal: 1 July 1999. (Ecuador 1–3 Argentina)
First European professional match: 4 February 2001. (Villarreal 2–0 Alavés)
First European professional goal: 11 February 2001. (Oviedo 1–3 Villarreal)
He is in the Guinness book of records for having missed three penalty kicks in the same match, against Colombia in the 1999 Copa América.
Palermo holds an Italian passport, which enables him to play as a UEFA player.
World Cup debut: 22 June 2010 in a match against Greece in the 2010 World Cup.
Oldest player to score for the Argentina national football team: 36 years and 7 months old, scored the second goal of Argentina's 2–0 win over Greece (This record was previously held by Diego Armando Maradona, who was 33 years old when he scored his last goal in a 1994 World Cup match, also against Greece).
Tied for 5th place of all time in a career among the Argentine Primera División top scorers with 227 goals (34 with Estudiantes and 193 with Boca Juniors).
1st place among Boca's all time top scorers with 236 goals, having surpassed the 221 goal mark of Roberto Cherro.
Top scorer in the professional era among Boca's top scorers with 236 Goals. (193 in Primera división Argentine tournaments and 43 in international tournaments)
Boca Junior's top scorer in international matches with 43 goals, 15 more than 2nd place Rodrigo Palacio.
As of 19 June 2011