An academy graduate of VfB Stuttgart, Werner represented the club at various youth levels. During the 2012–13 season, he was promoted to the U-19 team despite only being sixteen-years old at the time. He scored 24 goals for the campaign and was rewarded for his form when he won the Gold U-17 Fritz Walter Medal in 2013.

On 11 June 2016, Werner agreed to a four-year contract with RB Leipzig for a reported transfer fee of €10 million, the largest in the club's history. On 26 September 2016, he became the youngest player to play in 100 Bundesliga matches when he appeared in a fixture against FC Köln at the age of 20 years and 203 days. In doing so, he bettered the record previously held by Julian Draxler by 22 days, although he was again surpassed by Havertz in 2019. Werner ended the 2016–17 Bundesliga season with 21 goals, making him the leading German goalscorer in the division, and helped RB Leipzig qualify for the UEFA Champions League for the first time in the club's history.

On 18 June 2020, Werner agreed to sign for English Premier League club Chelsea, who activated his £47.5 million release clause, on a five-year contract. He joined the club on 1 July.