Born in Auckland, New Zealand, Vatuvei is of Tongan descent. He grew up in the same Otara neighbourhood as Ruben Wiki and attended Sir Edmund Hillary Collegiate. His cousin is Tongan-Japanese rugby union player Ruatangi Vatuvei. Vatuvei played for the Otara Scorpions and Otahuhu Leopards in Auckland Rugby League competitions before playing for the Otahuhu Ellerslie Leopards in the Bartercard Cup. When he was only 16 he joined the New Zealand Warriors development squad.
Vatuvei made his NRL debut for the New Zealand Warriors in Round 11 against the South Sydney Rabbitohs on the wing in the Warriors 26–12 win at Sydney Football Stadium. He played in 5 matches in his debut year.
In Round 4 against the South Sydney Rabbitohs at Mt Smart Stadium, Vatuvei scored his first NRL career try in the Warriors' 46–14 win. Vatuvei finished the year with him playing in 12 matches and scoring 9 tries for the Warriors. In the post season, Vatuvei made his international debut for New Zealand against Australia on the 16 October 2005. It was the opening game of the Tri-Nations, where the Kiwis beat the Kangaroos 38–28 at ANZ Stadium. Vatuvei later went on to play in the 2005 Tri-Nations final, scoring two tries on the way to a 24–0 victory over Australia at Alfred McAlpine Stadium in Huddersfield. Vatuvei played 5 matches and scored 3 tries in the series.
Vatuvei finished the 2006 NRL season with 10 tries from 18 matches. In the post season, he was selected for the New Zealand Tri-Nations squad playing in 5 matches and scoring 2 tries, including playing in the Kiwis 16–12 golden point extra time loss to Australia in the final.
Vatuvei was selected to play for the New Zealand on the wing in the 2007 Anzac Test match against Australia, scoring a try in the Kiwis 6–30 loss. After playing in 23 matches, Vatuvei was joint top try scorer for the Warriors alongside Jerome Ropati and Michael Witt with 10 tries in the 2007 NRL season.
Suffering a broken leg in Round 7 against the Gold Coast Titans, Vatuvei returned from injury to help the Warriors push for the playoffs. Needing to beat the Eels in the last round of the regular season, Vatuvei scored a hat-trick of tries, as the Warriors convincingly won 28–6 to qualify in 8th spot and book a match against minor premiers Melbourne Storm. In the finals series, The Warriors won 18–15 at Olympic Park, where the Storm had only lost twice in three seasons. Vatuvei scored one of the Warriors three tries and was denied another by a forward pass ruling. With the Warriors trailing 15–14 in the 78th minute, he received an offload from Jerome Ropati and busted several tackles over a run of 40m before passing to Michael Witt who sprinted 20m to score the match-winning try. Vatuvei scored another try in the Warriors 30–13 elimination semi-final victory over the Sydney Roosters at Mt Smart Stadium, the game that qualified the Warriors for the preliminary final against the Manly Sea Eagles, which they later lost 32–6 at SFS.
Vatuvei was named in the New Zealand squad for the 2008 World Cup. He went on to star in the tournament, breaking New Zealand's World Cup record for most tries in a match with four against England. Vatuvei went on to play in the first New Zealand team to win the World Cup, defeating Australia in the final. Vatuvei played in 5 matches and scored 4 tries in the tournament. He was named International Winger of the year in 2008.
Vatuvei was selected to play for New Zealand on the wing in the 2009 Anzac Test match against Australia, scoring a try in the 38–10 loss. The Warriors failed to make the finals, but Vatuvei finished the season as the club's top try-scorer with 13 tries in 19 matches in the 2009 NRL season.
On 13 February, Vatuvei played for the NRL All Stars in the inaugural All Stars match at Skilled Park. In Round 13 against the St George Illawarra Dragons at Mt Smart Stadium, Vatuvei played his 100th NRL career match as the Warriors lost 20–22. On 24 August, Vatuvei announced that he had extended his Warriors contract until the end of the 2013 season. Vatuvei surpassed Stacey Jones' club record of 77 tries in the first week of play-off matches against the Gold Coast Titans; the Warriors lost the match 28–16 at Skilled Park. He was the Warriors highest tryscorer for the 4th year in a row with 20 tries in 19 matches. In the post season, Vatuvei was selected for the New Zealand Four Nations squad.
Vatuvei scored his 90th NRL try for the Warriors in the 2011 NRL Grand Final against the Manly-Warringah Sea Eagles in the Warriors 24–10 losing effort, Vatuvei's first and only Grand Final appearance to date. He was the Warriors highest tryscorer for the 5th year in a row with 12 tries in 19 matches. Vatuvei missed the 2011 Four Nations series after failing medical tests.
On 4 February, Vatuvei played for the NRL All Stars in the 2012 All Stars match, scoring a try in the All Stars' 36–28 win. He played for New Zealand in the 2012 Anzac Test match as the Kiwis lost 12–20. Due to an injury to captain Simon Mannering, Vatuvei captained the side for several games between Rounds 21 and 25. In Round 24 against the Penrith Panthers at Mt Smart Stadium, Vatuvei played his 150th NRL career match in the Warriors 18–16 loss. In Round 23 against the North Queensland Cowboys at 1300SMILES Stadium, Vatuvei became the first player to score 100 tries for the club, in the Warriors shellacking 52–12 loss. Along with Shaun Johnson and Konrad Hurrell, Vatuvei was the New Zealand Warriors season's top try-scorer with 12 tries in 20 matches in 2012. Vatuvei, usually the Kiwis winger, was not picked for the October test against Australia.
On 8 May, Vatuvei extended his contract with the Warriors to the end of the 2015 season. He was the Warriors highest tryscorer for the 7th year in a row with 16 tries in 19 matches. Vatuvei was selected for the New Zealand World Cup squad. In the Kiwis opening game, a 42–24 win against Samoa at Halliwell Jones Stadium in Warrington, Vatuvei scored a hat-trick. Vatuvei played in the Kiwis 34–2 World Cup final loss against Australia at Old Trafford. He played in 4 matches and scored 4 tries in the series.
Vatuvei finished off the Warriors 2014 NRL season as the Warriors highest tryscorer for the year with 17 tries in 23 matches. On 7 October 2014, Vatuvei was selected in the New Zealand Kiwis' final 24 man squad for the 2014 Four Nations series. In the Four Nations final against Australia, Vatuvei scored two tries. With his second he became the new all-time top try scorer for the Kiwis, breaking Nigel Vagana's record of 19, a record held since 2006.
In the pre-season, Vatuvei played in the Warriors' Auckland Nines. On 13 February, Vatuvei was played for the NRL All Stars in the 2015 All Stars match, a 20–6 loss to the Indigenous All Stars. In Round 6, against the Wests Tigers, Vatuvei played his 200th NRL game, scoring twice in the Warriors 32–22 win at Mt Smart Stadium. In the following week against the North Queensland Cowboys, Vatuvei overtook Nigel Vagana as the most prolific New Zealand try scorer when he touched down for his 141st career try in the Warriors 28–24 loss at 1300SMILES Stadium.
Vatuvei was selected for New Zealand in the 2015 Anzac Test, scoring a try in the Kiwis' 26–12 win. In Round 14 against the Sydney Roosters, Vatuvei became the first player in NRL history to score at least 10 tries in 10 consecutive seasons. He suffered a season-ending shoulder injury in round 22,. Finishing the season with 16 matches and 11 tries for the Warriors.
In 2016, Vatuvei scored his 150th first grade try, the 11th player to do so.
On 6 May, Vatuvei made his debut for Mate Ma'a Tonga and scored a try in the 6th minute of the match in Tonga's 26-24 victory over Fiji at Campbelltown in the 2017 Pacific Test Triple Header. On 10 July, Vatuvei was released from his contract with the New Zealand Warriors and signed a deal with Salford Red Devils.. His last appearance for the Warriors was on 14th July 2017, in an emotional farewell at Mt Smart Stadium, temporarily renamed Manu Vatuvei Stadium for the match. Although he couldn't play in the match due to his new contract with Salford, he was given a team jersey and watched the match from the sidelines, often interacting with fans.