Mané was picked up from a football academy in Senegal by French side Metz and was a regular in the second half of the 2011/12 season but couldn't help his side avoid relegation. He was transferred to Red Bull Salzburg where he became a prolific scorer, averaging a goal every other game and winning a domestic double in 2013/14. An £11.8million move to Southampton followed and he scored ten goals from 32 appearances in all competitions, including the Premier League's fastest hat-trick in a 6-1 win over Aston Villa on 18 May 2015. His 176-second treble beat Robbie Fowler's record set in 1994, which stood at 276 seconds.

In 2015/16 Mané endured a barren spell of four months without a goal but this was ended with two against Liverpool as the Saints came from 2-0 down to win 3-2 on 20 March 2016. He went on to finish the season as their leading scorer and when Liverpool paid £30 million for him, he became the most expensive African footballer in history. Mané made a sensational start to his Reds career, scoring a stunning solo goal in a 4-3 win at Arsenal. He finished the season with thirteen league goals from 27 appearances with injury ruling him out of the end of the campaign. Memorable moments were the injury-time winner in the derby at Goodison Park and two goals in two minutes against Spurs at Anfield. The following season saw a major blow dealt when Mané was suspended for three games after being shown a straight red card early in the campaign at Manchester City. However, in the second half of the campaign, he excelled as part of a front three alongside Mo Salah and Robert Firmino. Mané scored his first Reds hat-trick against Porto in the Champions League round of sixteen and also netted Liverpool's goal in the 3-1 final defeat to Real Madrid

During 2018/19 Mané was exceptional, arguably more influential than Salah. He got crucial goals against Bayern Munich and Barcelona in the knockout stages of the Champions League and it was his pass that was handballed by Moussa Sissoko, earning a penalty in the first minute of the final. In the Premier League, Mané enjoyed his best-ever season, finishing with 22 goals to share the Golden boot with Salah and Arsenal's Pierre Aubameyang. Of the trio, however, only Mane's tally included no penalties. Mané's progress was rewarded in November 2018 when he signed a five-year contract, said to be worth £150,000 a week. ”I can’t think of a single club anywhere in Europe that wouldn’t want a player like Sadio available to them, so the fact he wants to remain with us says something about where we are currently,” said Klopp to liverpoolfc.com. “He is such an important member of our team and squad. He radiates joy and I think this is reflected in his performances and impact on the pitch. The only criticism I could ever have of Sadio is that maybe at times he is the only one not to see just how good he is but as an attacking player he is the complete package," Klopp added.

At the end of the 2018/19 season, Sadio Mané received a hero’s welcome as he linked up with the Senegal national team for the Africa Cup of Nations. Senegal went all the way to the final, only to suffer a narrow 1–0 defeat to Algeria. On 7 January 2020, Mané achieved his most prestigious individual accolade when he was named African Footballer of the Year for 2019 — a testament to his outstanding performances for both club and country. He signalled his intent for another memorable season early on, scoring both of Liverpool’s goals in the UEFA Super Cup final against Chelsea, as the Reds claimed the first of three trophies in their 2019/20 treble-winning campaign.

Graeme Souness, who had seen Ian Rush's brilliance up close during his own playing days at Liverpool, had high praise for Mané when the Premier League resumed after the Covid-19 lockdown: "Mané has fantastic attitude, he’s a warrior and it would be far easier to say what he hasn’t got, and I can’t tell you what he hasn’t got. He's spot on with his attitude, aggressive, will not be bullied. You could see he could deal with the English game [at Southampton] but then again it’s making the jump from Southampton, with all due respect, to a club that’s on the world stage where every game you play it could be the other team’s cup final. You don’t get easy games if you’re a Liverpool player. Everyone wants to go to war with you, everyone wants to take you on and everyone wants to beat you, you’re a scalp."

Souness added: "You don’t know how players will react until you get them in and he’s grown, he’s relished every challenge that comes his way and generally wins every challenge that comes his way. He’s a fabulous player, there is nothing to dislike about him. He’s smiley, open and you want to work with people like that.“I don’t think you’d have to say very much to him in terms of ‘train harder today’ or on match day ‘make sure you’re at it’ – I think it’s inbred in him. I think he’d be an absolute dream to work with.”

The 2020/21 season, however, was a more difficult one for Mané. With matches played behind closed doors due to Covid-19 and injuries to key players derailing Liverpool’s title defence, he struggled to match the exceptional standards of previous years. He also missed a spell after testing positive for the virus. Still, he ended the campaign on a high, scoring both goals in a 2–0 win over Crystal Palace on the final day — in front of 10,000 returning fans at Anfield — a result that secured Champions League football for the following season.

Mané bounced back in 2021/22, scoring 16 goals in 34 Premier League appearances. He also enjoyed international success, helping Senegal win the Africa Cup of Nations for the first time in their history. With just a year left on his contract and now 30 years old, Mané expressed his desire for a new challenge. On 17 June 2022, it was announced that he would join Bayern Munich. His time in Germany proved disappointing. He scored only 12 goals in 38 appearances and was involved in an unsavoury dressing room altercation with teammate Leroy Sané during a frustrating season. After just one year, he moved on again — this time joining Al Nassr in Saudi Arabia.

Mané’s first season in the Saudi Pro League saw him score 13 goals in 32 league appearances. Al Nassr also reached the King’s Cup final, but were beaten on penalties by Al Hilal.