Born in Alejandro Korn, Leto began his career with Buenos Aires club Lanús, making his first team debut on 25 June 2005.

Liverpool manager Rafael Benítez criticised the decision given the player's track record in the Champions League and national selection for the Olympics.

[10] On 28 July, Leto made his debut appearance for the greens on the away UEFA Champions League qualifying stages game against Sparta Prague, coming from the bench on the second half.

On 8 August in Athens, Panathinaikos needed a two-goal margin victory and Leto was one of the starting eleven for the Greek side who dominated the game 3–0 and qualified to the next round.

[14] Leto's good performances were enough for Serie B table-toppers Torino to report interest in the Argentine, as they look to regain status in the Italian top flight.

[15] On 30 October, Panathinaikos faced PAOK, Leto grabbed a goal as his side won 3–1 and maintained their lead at the top of the Greek first division.

[24][25] At the end of the loan, Cypriot club Anorthosis have made an offer for Sebastian Leto, but the Argentine left winger asked for a 48 hours deadline because he prefers to join Greek side Panathinaikos.

The manager of Palermo, Guillermo Barros Schelotto spoke about his compatriot and former player at Lanús, Sebastian Leto, and his desire to return in Greece for Panathinaikos.

Sebastian is a talented and clever player, with quality and still a future ahead of him, he will help Panathinaikos very much and maybe the next season decrease the difference from champions Olympiakos", said the 43-year-old Argentine at SDNA.

[27] On 5 February 2016, Panathinaikos officially announced the signing of Sebastian Leto until the end of the following season and the Argentinian left winger returned to the club after three years.

On 24 May 2017, thanks to a spot kick by the experienced Argentine attacking midfielder, Panathinaikos won a crucial game rivals AEK Athens at Leoforos Stadium, for the 2016-17 Playoffs.

[30] On 8 October 2017, Leto, (after Michael Essien, Rasmus Thelander, Jens Wemmer, Stathis Tavlaridis and Niklas Hult) became the latest player to file an appeal against Panathinaikos for late payment.