Keïta joined hometown club Horoya AC aged nine. He moved to France in 2012, joining the youth team of FC Istres after unsuccessful trials at FC Lorient and Le Mans FC.

In 2013, he was promoted to the first team of Istres. He made his Ligue 2 debut on 22 November 2013 against Nîmes Olympique. He scored 11 goals in 23 games in his first season as a professional, while his team were relegated to the Championnat National.

On 28 July 2013, Keïta made his international debut for the Guinea national team against Mali in a 2014 African Nations Championship qualification match. He came on as a half-time substitute for Naby Laye Camara in the 1–0 home win.

In 2014, he joined Austrian top division side Red Bull Salzburg. He made his league debut on 26 July 2014 against Wiener Neustadt. Keïta ended the season with five goals and two assists in 30 games, winning the league and cup double. The following season, he was selected as the Austrian Bundesliga Player of the Year.

Upon joining Liverpool, he was handed the number 8 shirt by Liverpool legend, Steven Gerrard, which had been vacated upon the departure of Gerrard to LA Galaxy in 2015. Keïta made his debut for Liverpool against West Ham United on 12 August 2018 and played a part in the opening goal for Mohamed Salah in a 4–0 win.

On 12 November 2015, he scored his first international goal, the only one away to Namibia in the first leg of the second round of 2018 FIFA World Cup qualification. Three days later in the return leg – in Morocco due to the Ebola virus epidemic in Guinea – he scored again in a 2–0 win.

In June 2016, Keïta moved to Red Bull Salzburg sister-club RB Leipzig, who had just been promoted to the German Bundesliga. He scored the winner on his league debut against Borussia Dortmund and scored seven more goals in his debut Bundesliga season. He was named in the league’s team of the season.

On 28 August 2017, a deal was struck for Keïta to join Liverpool on 1 July 2018 after the English club triggered his £48 million release clause in addition to paying an undisclosed premium. There would be no premium (£48 million total) if Leipzig did not qualify for European football, £4.75 million (£52.75 million total) if they qualified for the Europa League and £11 million (£59 million total) if they finished in the Champions League spots. Leipzig finished 6th in the Bundesliga, qualifying for the Europa League.

In 2017, Keïta was charged with uttering false documents. The German newspaper Bild reported that, in early December 2016 and again six weeks later, he had presented two fake Guinean driver’s licences in order to obtain a driving licence in Germany. The district court in Leipzig (Amtsgericht Leipzig) fined him €415,000, basing the sentence on Keïta’s estimated annual income of around €3 million. Keïta’s lawyer filed an appeal. The appeals court reduced the fine to €250,000.

On 5 April 2019, Keïta scored his first goal for Liverpool in a 3–1 win against Southampton, and added a first European goal four days later against FC Porto in the UEFA Champions League quarter-final first leg. He was injured in May 2019, ruling him out for the rest of the season. Although Keïta was injured, he won his first Liverpool title while out of the matchday squad as his team mates secured the win in the Champions League final against Tottenham Hotspur in early June.

On 18 December, he scored the opening goal in a 2–1 win over Mexican club Monterrey as Liverpool progressed to the Club World Cup final; three days later, on 21 December, he started in the final against Flamengo, playing 100 minutes until being substituted as Liverpool won 1–0 to be crowned world club champions. On 2 January 2020, he was named in the starting lineup against Sheffield United, but was withdrawn after sustaining a groin injury during the warm-up, being replaced by James Milner.