He's an aggressive right-handed batsman and has gained attention from selectors and fans through his strokeplay and high runs scoring in Indian domestic cricket. Because of his front foot play and ability to attack the bowler by charging down the pitch, many have compared his batting style to England's Kevin Pietersen. Tiwary was named in the ODI squad to Bangladesh, however he failed to make the playing eleven after sustaining an injury in training, the morning he was supposed to debut. He eventually made his debut against Australia in the 2007–08 Commonwealth Bank Series in which he scored only 2 runs in his only innings. He was later included in the India team for the West Indies tour of 2011, as a replacement for Yuvraj Singh, who opted out of the series due to a lung infection. Manoj Tiwary played the 4th and 5th ODI in the series. He later got picked for England's tour of India in October. He played in the 5th ODI and got 24 runs. He also played the only T20 and scored 15 runs. Tiwary was subsequently named in the squad for the ODI's against West Indies in November–December. He played in the 5th ODI at Chennai when India was down by 2 wickets for only 1 run in the very first over of the match. He then went on build a solid innings which got him his scoring maiden ODI century despite having cramps and retired soon after getting his century. Eventually India won the match by 34 runs and he was awarded the Man-Of-The-Match for this match-winning knock. Even after the unbeaten century, Tiwary was made to sit in the reserves for 14 successive matches following the century. However, he made an auspicious comeback as an all-rounder replacing leg spinnerRahul Sharma against Sri Lanka at Colombo as he took 4/61 from his 10 overs with his leg-breaks to restrict the hosts to 251/8. He took the wickets of Dinesh Chandimal, Angelo Mathews, Jeevan Mendis and Thisara Perera, and followed it with a fighting 21 from 38 at a tough time coming at 60/3. India eventually won the match as Virat Kohli scored an unbeaten ton. Tiwary also was picked for the Commonwealth Bank tri-series against Australia and Sri Lanka, but he didn't play any matches. Manoj Tiwary was again selected in the Indian team for the Asia Cup 2012 where again he didn't play any matches. Tiwary was also selected for the lone T20 against South Africa which was played celebrating 150 years of settlement of Indians in South Africa. In October 2017, he played in his 100th first-class cricket match, in the fixture between Bengal and Chhattisgarh in the 2017–18 Ranji Trophy. He was the leading run-scorer for Bengal in the 2018–19 Vijay Hazare Trophy, with 366 runs in nine matches. In October 2018, he was named in India B's squad for the 2018–19 Deodhar Trophy. In November 2018, batting for Bengal against Madhya Pradesh in the 2018–19 Ranji Trophy, he scored his fifth double-century in first-class cricket. In January 2020, in the 2019–20 Ranji Trophy, he scored his maiden triple century in first-class cricket, with an unbeaten 303 runs.
Tiwary was signed by the Delhi Daredevils for a sum of US$675,000 in the initial seasons of the Indian Premier League. He was traded to the Kolkata Knight Riders in exchange for Moises Henriques before the 2010 IPL season. In the auction for 4th edition of the Indian Premier League, he was signed by the Kolkata Knight Riders for a sum of US$475,000. In the fourth as well as the fifth season of the IPL, he has been a permanent fixture in the Kolkata Knight Riders middle order. In the final of IPL 2012, Manoj Tiwary hit the winning runs off the bowling of Dwayne Bravo to help Kolkata Knight Riders win the title. In IPL 2013, he played in 10 matches and scored just 146 runs at an average of 18.25. In February 2017, he was bought by the Rising Pune Supergiants team for the 2017 Indian Premier League for 50 lakhs. In January 2018, he was bought by the Kings XI Punjab in the 2018 IPL auction for Rs 1 Crore.