Vijay was taken on the tour of Bangladesh in January 2010 as the reserve batsman, and he was called into the team after V. V. S. Laxman injured a finger in the First Test. Vijay played in the Second Test in Mirpur in Laxman's No. 5 position, scoring 30. In the same match, No. 3 batsman Rahul Dravid was injured after being hit under the jaw by a bouncer, so Vijay then played in Dravid's position in the two-Test home series against South Africa.
He was later selected as the reserve opener for away series against Sri Lanka in August 2010 and the home series against Australia in October 2010. He played in the Second and Third Tests against Sri Lanka after Gambhir was injured. He got another opportunity when Gambhir, was injured in the first match against Australia and was ruled out of Second Test. Vijay scored 139 runs in the first innings, his maiden Test century, featuring in a triple century partnership with Sachin Tendulkar. Vijay and debutant Cheteshwar Pujara added 72 runs crucial partnership which helped India complete a 2–0 series win.
Vijay debuted in ODIs against South Africa in the third and final one dayer on 27 Feb 2010. He scored a brisk 25 runs off 16 balls.
Vijay played for IPL franchise from his home town Chennai Super Kings till the sixth edition and represented Delhi Daredevils in IPL7. He was one of the key performers for Chennai in the 3rd edition of IPL in 2010 when Chennai were crowned champions. His first century for Chennai Super Kings was in the third season where he scored 127 runs off 56 balls against the Rajasthan Royals. He was awarded the Man of the Match. In the same year, Vijay had prolific run in the Champions League T20 held in South Africa. Vijay was the top scorer of the tournament with 294 runs. He was instrumental in Chennai winning the cup.