೧೫ನೇ ವಯಸ್ಸಿನಲ್ಲಿ ಮೆರಡೋನ ಅರ್ಜೆಂಟಿನೋಸ್ ಜೂನಿಯರ್ಸ್ ತಂಡದಲ್ಲಿ ಪಾದಾರ್ಪಣೆ ಮಾಡಿ ೧೯೭೬ರಿಂದ ೧೯೮೧ರವರೆಗೂ ಅಲ್ಲೇ ಆಡುತ್ತಿದ್ದರು. 

ಅರ್ಜೆಂಟಿನಾ ರಾಷ್ಟ್ರೀಯ ಫುಟ್‍ಬಾಲ್ ತಂಡಕ್ಕೆ, ತಮ್ಮ ಹದಿನಾರನೇ ವಯಸ್ಸಿನಲ್ಲಿ, ಹಂಗೇರಿ ದೇಶದ ವಿರುದ್ಧ ಆಡುವುದರ ಮೂಲಕ ಪಾದಾರ್ಪಣೆ ಮಾಡಿದರು. 
ಹದಿನೆಂಟನೆಯ ವಯಸ್ಸಿನಲ್ಲಿ 'ಫುಟ್‍ಬಾಲ್ ವರ್ಲ್ಡ್ ಯೂತ್ ಚಾಂಪಿಯನ್‍ಷಿಪ್' ಪಂದ್ಯಾವಳಿಯಲ್ಲಿ ಅರ್ಜೆಂಟೀನಾ ದೇಶದ ಪರವಾಗಿ ಆಡಿದರಲ್ಲದೆ, ಫೈನಲ್ ಪಂದ್ಯದಲ್ಲಿ ಸೋವಿಯತ್ ಒಕ್ಕೂಟ ತಂಡದ ವಿರುದ್ಧ ೩–1 ಅಂತರದಲ್ಲಿ ಜಯ ಸಾಧಿಸಲು ಕಾರಣರಾಗಿ, ಆ ಪಂದ್ಯಾವಳಿಯ ತಾರೆಯಾಗಿ ಹೊರಹೊಮ್ಮಿದರು.

೧೯೮೨ರಲ್ಲಿ ಮರಡೋನ ತಮ್ಮ ಪ್ರಥಮ ವಿಶ್ವಕಪ್ ಪಂದ್ಯಾವಳಿಯನ್ನು ಆಡಿದರು. ಮೊದಲನೇ ಸುತ್ತಿನಲ್ಲಿ ಚಾಂಪಿಯನ್ ತಂಡ ಆರ್ಜೆಂಟೀನಾ ಬೆಲ್ಜಿಯಂ ತಂಡಕ್ಕೆ ೦-೧ ರಿಂದ ಸೋತಿತು. ನಂತರ ಹಂಗರಿ ಮತ್ತು ಎಲ್ ಸಾಲ್ವಡಾರ್ ಗಳನ್ನು ನಿರಾಯಾಸಕರವಾಗಿ ಸೋಲಿಸಿ ದ್ವಿತೀಯ ಸುತ್ತಿಗೆ ಪ್ರವೇಶಿಸಿತಾದರೂ ಅಂತಿಮವಾಗಿ ವಿಶ್ವಕಪ್ ಗೆದ್ದ ಇಟಲಿ (೧-೨) ಮತ್ತು ಮರಡೋನಾರನ್ನು ಹೊರಕ್ಕೆ ಕಳುಹಿಸಿದ ಬ್ರೆಝಿಲ್ ವಿರುದ್ಧ ಪಂದ್ಯ (೧-೩) ಗಳ ವಿರುದ್ಧ ಎರಡನೇ ಸುತ್ತಿನಲ್ಲಿ ಸೋತಿತು. 
Later in the year, Maradona was transferred to FC Barcelona. In 1983, under coach César Luis Menotti, Barcelona and Maradona won the Copa del Rey (Spain's annual national cup competition), beating Real Madrid. However, Maradona had an unhappy tenure in Barcelona: first a bout with hepatitis, and then an ill-timed tackle by Athletic Bilbao's Andoni Goikoetxea that put Maradona's career on the line; Diego's physical strength and willpower made it possible for him to be back on the pitch after only 14 weeks. It is said that while playing for Barcelona, Maradona was introduced to cocaine, to which he would become an addict.
Barcelona's management was not satisfied with Maradona, and in 1984 transferred him to SSC Napoli, where he became an adored star, lifting the team to its most successful era. Napoli won their only Italian Championships (1986/87 and 1989/1990), a Coppa Italia (1987), a UEFA Cup (1989) and an Italian Supercup (1990). Napoli were also runners-up in the Italian Championship twice (1987/88 and 1988/89).

Maradona led the Argentine national team to victory in the , the team winning 3–2 in the final against West Germany. Throughout the 1986 World Cup, Maradona asserted his dominance and was widely regarded as the best player of the tournament. However, it was the two goals he scored in the quarter-final game against England which cemented his legend. Action replay footage showed that the first goal was scored with the aid of his hand. He later claimed it was the "Hand of God" and described it as "A little of the hand of God, and a little of the head of Maradona," implying that God was ultimately responsible for the goal, because the referee had missed the handball offense. However, on 22 August 2005 Maradona acknowledged on his television show that he hit the ball with his hand purposely and that he immediately knew the goal was illegitimate. He recalled thinking right after the goal that "I was waiting for my teammates to embrace me, and no one came . . . I told them, 'Come hug me, or the referee isn't going to allow it.'" 

In contrast, however, Maradona's second goal was an uncontroversial and impressive display of footballing skill. He ran half the length of the pitch, passing five English players (Glenn Hoddle, Peter Reid, Kenny Sansom, Terry Butcher, and Terry Fenwick) as well as goalkeeper Peter Shilton. This goal was voted Goal of the Century in a 2002 online poll conducted by FIFA. Argentina went on to defeat England 2-1 in that game. The two goals were ranked 6th in the 100 Greatest Sporting Moments in 2002 by the UK's Channel 4 television channel. 

He followed this with another miraculous goal in the semi-final against Belgium. In the final the opposing German side attempted to subdue him by double-marking but he nevertheless found the space to lay on the winning goal for Jorge Burruchaga.

Maradona also captained Argentina in the , leading his team to the final, where they lost 1–0 to West Germany. He arrived at the and played two games (scoring one goal) before being sent home after failing a drug test for ephedrine doping. On this matter, he has suggested that he had an agreement, on which FIFA later reneged, to allow him to use the drug for weight loss before the competition in order to be able to play, so that the World Cup would not lose prestige because of his absence. This allegation was never proved, and many attribute his comment ("they cut off my legs") to Diego's anger at being suspended.

In Naples Maradona transformed the local club, SSC Napoli. Traditionally they had been overshadowed by the teams from the industrial cities in the north, but Maradona's arrival (along with Careca and others) brought them a first scudetto, followed by a second in 1989, and cup successes. However, he also faced a scandal there regarding an illegitimate son and was the object of some suspicion over his friendship with the Camorra, the local mafia.

Maradona left Napoli in 1992, after serving a 15-month ban for failing the drug test for cocaine, and played for Sevilla FC (1992–93), Newell's Old Boys (1993) and Boca Juniors (1995–97). He also attempted to work as a coach on two short stints, leading Mandiyú of Corrientes (1994) and Racing Club (1995) without much success. He retired from football on October 30, 1997.

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