Reus was born in Dortmund, North Rhine-Westphalia. He began to play football for his hometown club Post SV Dortmund in 1994 and joined the youth ranks of Borussia Dortmund in 1996. He played for Borussia Dortmund until he left for the U-19 team of Rot Weiss Ahlen in the summer of 2006. During his first year there, he played as an attacking midfielder and was featured in five games for the club’s second team, which played in the Westphalia league at the time. He scored a goal in each of his first two games. The following year, he was able to break into Ahlen’s first team, which played in the German third division at the time. He started twice and was featured in 14 matches, scoring two goals. One of his goals came on the last day of the season and propelled the team being promoted to the 2. Bundesliga. In 2008–09, as a 19-year-old, he had his definitive breakthrough as a professional football player, playing 27 games and scoring four goals.

On 25 May 2009, Reus signed a four-year contract with Bundesliga club Borussia Mönchengladbach. On 28 August 2009, he scored his first Bundesliga goal in a game against Mainz 05 after a 50-metre solo run, and since then became a prolific goalscorer for his club under Lucien Favre. At the start of the 2011–12 season, Reus began the season in fine form, scoring 7 goals in 12 matches. His contract with Gladbach was set to expire in 2015 and reportedly had a buy-out clause of €18 million. Reus mentioned that his role model was Tomáš Rosický.

On 11 August 2009, Reus made his Germany under-21 debut in a friendly match against Turkey. On 6 May 2010, he earned his first call-up to the senior team for a friendly match against Malta on 14 May 2010. On 11 May 2010, he withdrew from the squad due to a leg injury picked up in the last game of the season against Bayer Leverkusen. On 7 October 2011, he made his debut against Turkey. He scored his first goal for the team on 26 May 2012 in a 5–3 defeat to Switzerland. On 22 June, he scored in the UEFA Euro 2012 quarter-final against Greece, his first start for Germany in the tournament.

Reus dated Carolin Bohs in 2009. They broke up in 2013 but remain close friends. Reus started dating German model Scarlett Gartmann in December 2015. Together they had their first child in March 2019 and got married later the same year.

On 4 January 2012, Reus signed with his former club Borussia Dortmund for a €17.1 million transfer fee on a five-year deal. He spoke about his transfer saying, “I’ve made the decision to take the next step forward in the coming season. I’d like to play for a club who can challenge for the league title and guarantee me Champions League football. I see this chance in Dortmund.” Reus officially re-joined Dortmund on 1 July 2012. In Reus’s Bundesliga debut with Dortmund on 24 August, he scored a goal as his new side completed a 2–1 win over Werder Bremen. On 29 September, Reus scored two goals for Dortmund in a 5–0 rout of his former club Borussia Mönchengladbach, pushing the champions to the top of the Bundesliga table through six games.

Reus is renowned for his versatility, speed, agility, technical skills, intelligence, and shooting ability; however he is also known for his proneness to injury. In 2012, Franz Beckenbauer spoke about Reus, along with Mario Götze, saying, “…as a classic duo there is nobody better than the prolific Reus and Götze.” Reus was voted the Footballer of the Year (Germany) in 2012 and was named in the UEFA Team of the Year in 2013. In 2013, he was ranked as the fourth best footballer in Europe by Bloomberg. Although he is highly regarded for his attacking movement, powerful finishing with either foot in open play, timing, and eye for goal, as well as his accuracy from set pieces, Reus is also a hard-working player and a precise passer, who possesses good vision, which enables him to create chances and provide assists to teammates, in addition to scoring goals himself. As such, Reus is a versatile forward, who is capable of playing in several offensive positions, and has been deployed as a second striker, in a central role as an out-and-out striker (although this is not his favoured position), as a winger on either flank (although he favours the left side, as it allows him to cut inside onto his stronger right foot), and also in a central attacking midfield role as a number 10.

On 16 February 2013, Reus scored a hat-trick, netting all the goals in Dortmund’s thumping of Hessian side Eintracht Frankfurt. On 11 May, Reus scored a late brace against VfL Wolfsburg to help Dortmund draw the match after being two goals down.

On 9 April 2013, Reus scored an injury time goal which was a vital one in the stunning injury time comeback against Malaga in the quarter final leg 2 of UEFA Champions League. Dortmund won the match by 3-2 and progressed on to the next round where they defeated Real Madrid 4–3 on aggregate to reach the final.

On 27 July 2013, in the 2013 DFL-Supercup against Bayern Munich, Reus netted the game’s opening goal and later rounded off the scoring, as Borussia Dortmund claimed a 4–2 victory to lift the trophy.

On 18 August, Reus converted a penalty kick which rounded off the scoring as Dortmund defeated Eintracht Braunschweig 2–1 at the Signal Iduna Park in the second game of Dortmund’s 2013–14 league campaign. He then scored a brace against SC Freiburg, one from the penalty spot, and started the season hitting impressive form. Reus had confirmed he would be Dortmund’s penalty taker for the season, though despite winning a penalty against 1860 Munich in the DFB Pokal, he allowed teammate Pierre-Emerick Aubameyang in taking the penalty which propelled the Borussia-based club into the next round of the competition. On 1 November 2013, Reus scored a goal for Dortmund in a 6–1 win against VfB Stuttgart in the Bundesliga.

On 25 February 2014, Reus scored a goal in a 4–2 win for Dortmund against Zenit Saint Petersburg in the first leg of the round of 16 in the UEFA Champions League. On 29 March, he then scored a hat-trick in a 3–2 win for Dortmund against VfB Stuttgart in the Bundesliga. On 8 April, Reus scored twice in Borussia Dortmund’s second leg 2–0 win against Real Madrid, though Dortmund were eventually knocked out of the competition after losing 3–2 on aggregate. Reus finished the season with 23 goals and 18 assists in all competitions.

In the second match of the 2014–15 Bundesliga against FC Augsburg, Reus scored one goal and helped set up another. Dortmund went to win the match by 3–2. In September 2014, he was diagnosed with an ankle injury. On 22 October 2014, having returned from injury, Reus contributed a goal and assist in their 4–0 Champions League group stage away win against Galatasaray. On 1 November, he scored the only goal for Dortmund in their 2–1 away loss against their rivals Bayern Munich.

Reus established himself as a regular member of Joachim Löw’s side in the 2014 FIFA World Cup qualification campaign, scoring five goals and registering three assists in six matches. He was named in Germany’s squad for the World Cup finals, but was ultimately forced to withdraw after suffering an ankle injury in the team’s 6–1 warm-up win against Armenia on 6 June.

Reus made his international comeback in Germany’s first post-World Cup friendly against Argentina on 3 September 2014. However, the world champions were defeated 4–2 by the side they had beaten in the World Cup final two months earlier.

In December 2014, Reus was fined €540,000 for driving without a valid licence, which constitutes a felony in Germany. The fine was based on his then monthly salary of €180,000. He had been driving for years with a fake Dutch licence, a felony in its own right, and has been issued with speeding tickets on at least five occasions since 2011 without authorities knowing that he was not legally licensed. The felony charges for using a counterfeit licence were later dropped causing some controversy and raising questions from politicians whether his celebrity status had been a reason for a milder sentence. When convicted, Reus said, “The reasons I did it are something I cannot really understand.” Prior to his conviction, he had appeared in commercials for cars and petrol. In August 2016, Reus confirmed that he now has a driver’s licence.

On 10 February 2015, Reus signed a contract extension with Dortmund, keeping him at the club until 2019.

On 5 August 2015, Reus scored a goal in Borussia Dortmund’s 5–0 win against Wolfsberger AC to advance into the 2015–16 Europa League play-off round. On 15 August, he then opened the 2015–16 league campaign with a goal and an assist in a 4–0 home win against his former club Borussia Mönchengladbach. On 28 August 2015, he scored a hat-trick in their 7–2 home win against Odds BK to qualify for the 2015–16 UEFA Europa League.

On 20 April 2016, Reus was one of three goalscorers as Borussia won 3–0 away at Hertha BSC in the semi-final of the DFB-Pokal. Before the start of the 2016–17 Bundesliga, he became the captain for Borussia Dortmund shortly after former club captain Mats Hummels left for rivals Bayern Munich. He finished the 2015–16 season with total of 23 goals and 8 assists in 43 appearances.

After being sidelined due to injury, Reus made his return on 22 November 2016. He scored twice and assisted once in a historic 8–4 Champions league group stage win against Legia Warsaw. Reus took the game ball for it was originally a hat-trick game by him. On 3 December 2016, he assisted three goals in their 4–1 win against his former club Borussia Mönchengladbach. Four days later, Reus scored in a 2–2 draw against Real Madrid; Dortmund subsequently advanced to the round 16 as the winners of Group F, ahead of Madrid. On 10 December 2016, Reus continued his goalscoring form with a late equaliser in Dortmund’s 1–1 draw with 1. FC Köln.

During the 2017 DFB-Pokal Final, Reus suffered a partial cruciate ligament tear and was substituted at halftime. Dortmund went on to win the match, giving Reus his first major trophy. The initial prognosis suggested that he would miss “several” months.

On 10 February 2018, Reus recovered from the ligament damage and made his return against Hamburg in the Bundesliga. Reus scored his first goal since his return from injury and the only goal in the match against his former club Borussia Mönchengladbach in a 1–0 victory. Reus scored Dortmund’s only goal in two consecutive matches against Augsburg and RB Leipzig in which both the matches ended in a 1–1 draw. On 9 March 2018, Reus extended his contract with the club until 30 June 2023. On 21 April, Reus scored twice in a 4–0 win over Bayer Leverkusen, where he also missed a penalty. On 29 April, Reus scored a 19th-minute goal in Dortmund’s 1–1 draw with Werder Bremen. On 12 May 2018, Reus scored the only goal for the team in Dortmund’s 3–1 loss to Hoffenheim. Reus finished the season with 7 goals in 15 appearances in all competitions.

Prior to the start of the 2018–19 season, Reus was made club captain by incoming coach Lucien Favre. On 21 August 2018, Reus scored the winning goal in extra time to help his side earn a 2–1 victory over SpVgg Greuther Fürth in the DFB-Pokal first round match. Reus scored a 90th-minute goal which was his 100th Bundesliga goal as Dortmund defeated RB Leipzig with a 4–1 victory. On 27 September, he scored two goals including his 100th goal for Borussia Dortmund across all competitions in a 7–0 victory over 1. FC Nürnberg.

On 10 November 2018, he scored back to back goals in the second half of Der Klassiker against Bayern Munich as Dortmund came from behind to win the match 3–2. The game kept Dortmund on top of the Bundesliga table, 7 points ahead of Bayern Munich.

On 2 June 2018, Reus made his return to international duty after two years in a friendly match against Austria, which ended in a 2–1 loss for Germany. Reus was included in Joachim Löw’s 23-man final squad for the 2018 FIFA World Cup on 4 June 2018. On 17 June, Reus made his first World Cup appearance during their opening match against Mexico as a substitute by replacing Sami Khedira in the 60th minute, but the match ended in a 1–0 loss for Germany. On 23 June, Reus scored an equalizing goal and his first World Cup goal in the second half as Germany defeated Sweden with 2–1 victory in their second group stage match to resurrect their World Cup hopes. He also provided an assist to Toni Kroos’s late winning goal in that match and was named Man of the Match. However, his side were knocked out from the tournament after losing 2–0 to South Korea in their last group stage match on 27 June.

In March 2020, Reus and his wife, Scarlett, donated €500,000 to people and smaller businesses in need in his hometown of Dortmund during the 2019–20 coronavirus pandemic.