Sehwag had his international breakthrough in Sri Lanka in August 2001 when he was promoted to the opening slot for the tri-series also involving New Zealand. The promotion to open the innings came because regular opener Sachin Tendulkar was absent due to a foot injury. In the match against New Zealand that was to decide the finalist, he scored his maiden century from 69 balls. At the time, the century was the third fastest ODI century for an Indian behind Mohammad Azharuddin's 62 ball effort and Yuvraj Singh's 64 ball effort. This was his first score beyond 50 in ten matches and saw him named the Man of the Match. This performance earned him a regular spot in the ODI squad in the middle-order. He bettered his own record by hitting a 60-ball century against New Zealand during the 2009 tour. An innings of note in 2002 was the 22 ball half-century against Kenya in Bloemfontein, tying the second fastest 50 by an Indian. Because of his attacking cricket stroke plays, Sehwag has got many fans, including the WestIndies legend Desmond Haynes, who admitted that he is a great fan of him.
Sehwag's maiden century in mid-2001 in Sri Lanka was not enough to gain selection in the Test team for the corresponding series. Sehwag made his Test debut in late 2001 in the First Test against South Africa in Bloemfontein as a middle-order batsman. He scored 105 on debut despite the South African win. He was given a one-match suspension by ICC match referee Mike Denness for overappealing in the Second Test in Port Elizabeth, which led to political dispute amongst the ICC and the two countries. He returned for the home series in 2001–02 against England and Zimbabwe. After scoring two half-centuries in the preceding series, he was promoted to a makeshift opener on the 2002 England tour after the failure of previous openers and an experiment with wicket-keeper Deep Dasgupta. He scored 84 in the new role at Lord's and then a century in the Second Test at Trent Bridge, and has batted there in Test matches ever since. He scored his maiden home century of 147 in the First Test against the West Indies in 2002–03 home season in Mumbai, which was at the time his top score in Test matches, earning him his first man of the match award. After a poor tour to New Zealand, he scored passed 50 for the first time in 9 innings when he scored 130 in a Test at Mohali against New Zealand in late 2003 .
In November 2001, Sehwag was involved in controversy in the Second Test match between India and South Africa at St George's Park, Port Elizabeth, when he was given a one Test ban for "excessive appealing" by ICC Match referee Mike Denness. He was one of six Indian players to receive bans, four of which were suspended bans. The unprecedented severity of the bans precipitated an international cricketing, political and administrative crisis, with the Indian cricket establishment threatening to call off the tour unless Mike Denness was removed as match referee from the third test match. ICC backed Mike Denness and the South African board backed the Indian cricket establishment and did not allow Mike Denness to enter the stadium on the first day of the third test match. ICC declared that the match was 'unofficial' and 'friendly five day match' and the series was officially declared as a 2 match series and South Africa as 1–0 winners. The subsequent England tour to India was placed in jeopardy when India picked Sehwag in the Test squad. Subsequent to this development, ICC issued a warning that any match with Sehwag in the cricket team will not be considered an "official" Test match until Sehwag had served his one match ban. After negotiations with ECB and ICC and in general interest of cricket, Sehwag was dropped from the team for the first Test against England. In October 2015, Sehwag told to Zee News " I was planning to retire in 2007 when dropped from the team but Tendulkar stopped me from doing so."
Sehwag's aggressive batting has found success at the top of the batting order. He has scored centuries (100 or more runs) on 22 occasions in Test cricket and in 15 One Day International (ODI) matches. In Tests, Sehwag has scored centuries against all the Test-cricket playing nations except Bangladesh and Zimbabwe, and is sixth on the list of leading Test century makers for India. In 2001, he became the eleventh Indian player to score a century on Test debut, with 105 runs against South Africa. His centuries have been scored at fourteen cricket grounds, eight of which were outside India. He has made six scores of 200 runs or more, the most by an Indian batsman, of which a record three have come against Pakistan. Sehwag is the only Indian to have scored a triple century (300 or more runs), and has done so twice—309 against Pakistan in Multan in 2004 and 319 against South Africa in Chennai in 2008, the later being the fastest triple century in Test cricket with 300 coming up off just 278 balls. In ODIs, Sehwag's maiden century was made against New Zealand at the Sinhalese Sports Club, Colombo in 2001. His highest score of 219, the highest ODI score ever, was made against the West Indies at the Holkar Cricket Stadium in Indore. He has been dismissed five times in the nineties.