Wanyama attended Kamukunji High School, which fields a successful football team. Upon leaving High School, he also played with JMJ Academy for three years during which time he also joined Kenyan Premier League clubs Nairobi City Stars and AFC Leopards. In 2007, he joined Allsvenskan club Helsingborg but after the departure of his brother McDonald Mariga to Serie A side Parma in 2008, Wanyama returned to Kenya.

Wanyama made his debut for the Kenyan national team in May 2007, aged just 15 in a friendly against Nigeria. He also played in all six of Kenya’s 2010 FIFA World Cup qualifiers. He became the captain of his national team in 2013. Represented the national team at the 2019 Africa Cup of Nations.

After a successful trial, Wanyama signed for Beerschot AC on a four-year contract in summer 2008. He made his debut in a League match at the end of the 2008–09 season. In September 2009, he was fined €100 and given a three-match suspension for a violent tackle on Matías Suárez of Anderlecht.

Wanyama scored his first goal for Beerschot on 11 December 2010, a 77th-minute equaliser against Westerlo. In April 2011, he received another three match suspension after video evidence showed he had elbowed Brecht Dejaeghere of K.V. Kortrijk.

On 9 July 2011, Wanyama finally completed a £900,000 move to Celtic, after the Scottish club had failed to sign him the previous year. He signed a four-year contract and in doing so became the first ever Kenyan to play in the SPL. Wanyama chose 67 as his squad number to honour the Lisbon Lions, Celtic’s 1967 European Cup-winning team. Wanyama made his Celtic league debut in a 1–0 loss to St Johnstone on 21 August 2011. He played in central defence rather than his favoured central midfield role. He came on as a late substitute in a 4–0 win over Motherwell, and played for the whole second half in a 2–0 League Cup win over Ross County. On 29 September 2011, he started in Celtic’s 1–1 draw with Italian team Udinese in the Europa League. This was his first European match for the club. On 10 December 2011, Wanyama scored his first goal for Celtic in a 1–0 win over Hearts at Celtic Park, a tremendous 25-yard strike which hit the top corner. His performances during December earned him the Scottish Premier League young player of the month award. He scored his second Celtic goal on 2 January 2012 in a 3–0 win against Dunfermline at East End Park. Wanyama scored in Celtic’s 2–1 win against Dundee United at Celtic Park and in the 4–0 victory against Hearts at Tynecastle.

On 20 October 2012, Wanyama scored twice against St Mirren at St Mirren Park, the second of which was a half volley from 25 yards out. On 25 October, Wanyama’s agent released a statement saying that he had turned down an improved contract offer from Celtic, stating that his wage demands could not be met by the club amid speculation of interest from clubs in England. On 7 November, Wanyama opened the scoring with a powerful header as Celtic shocked Barcelona in the Champions League group stage, by beating them 2–1 at Celtic Park.

After much speculation and a previous breakdown in talks, on 11 July 2013, Wanyama signed for Premier League side Southampton for a fee claimed to be £12.5 million, making him the first Kenyan to ever play in the Premier League.

He made his debut on 17 August 2013, in a 1–0 away win against West Bromwich Albion. Wanyama made 24 appearances in his first season, but injuries hindered his efforts to make much of an impact in the team.

Under new manager Ronald Koeman, Wanyama came into his own in the 2014–15 season. He scored his first goal for the club in a 1–0 league victory over Swansea City at the Liberty Stadium on 20 September 2014, after replacing James Ward-Prowse in the 69th minute. His next goal came in an 8–0 trouncing of Sunderland on 19 October 2014. Wanyama would score his third goal for the Saints in spectacular fashion, a 40-yard shot after Eldin Jakupović’s poor clearance fell straight to him, in what proved to be the only goal in a win over Hull City. His performances saw him awarded the league’s African Player of the Month for September, with him stating “It is wonderful being recognised as someone who has done well for his club.”

In 2015, Wanyama participated in the production of a short film about football in Kenya called Mdudu Boy, written and directed by actress Ella Smith.

On 23 June 2016, Premier League club Tottenham Hotspur announced that they had reached an agreement with Southampton for the transfer of Wanyama, signing a five-year contract for a fee of £11 million. Wanyama had previously worked with Tottenham manager Mauricio Pochettino who brought him to Southampton in July 2013. Wanyama scored his first goal for the club on his home debut against Crystal Palace, in the 82nd minute of a 1–0 league win for Spurs. The goal made him the 138th different player to score for the club, extending its record for the most variety of goalscorers for a single club in the Premier League.

Early in the 2017–18 season, Wanyama injured his knee in the match against Chelsea and was sidelined for over four months. He returned to training in mid-December. On 2 January 2018, he made his first appearance after his injury, as a substitute in the away match against Swansea City. His equalizer in Tottenham’s 2–2 draw with Liverpool on 4 February 2018 was voted the Premier League Goal of the Month.

On 3 March 2020, Tottenham announced that it had agreed to transfer Wanyama to Major League Soccer club Montreal Impact, where he will become a Designated Player.

On 11 March 2020, Wanyama made his competitive debut for Montreal at Stade Olympique in the first leg quarterfinal of the CONCACAF Champions League where he was named in manager Thierry Henry’s starting side. Wanyama provided an assist to Saphir Taïder – who Wanyama was briefly teammates with at Southampton in 2014 – in a 1–2 defeat by Honduran champions C.D. Olimpia.