In 2001 West Bengal Legislative Assembly election, he was TMC candidate from Jagatdal constituency and got 56,741 votes but lost.

On 11 July 2011, when Prime Minister Manmohan Singh directed Mukul Roy to visit the site of the derailment of the Guwahati-Puri Express in Assam, he openly defied him.

This brought a lot of displeasure among the political circles and he was shunted out of the Railways portfolio in the latest cabinet reshuffle on 12 July 2011.

This happened after Mamata Banerjee expressed her discontent with the increase in passenger fares, and demanded the resignation of Dinesh Trivedi, Railway Minister.

With the exit of Trinamool from UPA coalition due to an allowance of 51% FDI in retail and aviation sector, Mukul Roy's tenure of railway minister came to an end in the month of September 2012.

[15] Roy ran a special train called "DU Gyan Uday Express" a Bengali worded statement, which took 1000 students of Delhi University to places like Ahmedabad, Mumbai, Goa and Bangalore during the summer break of 2012.

[16][17] An application has been submitted to the Election Commission for the formation of the new political party called All India Trinamool Congress and Mukul aide Amitabha Majumdar has been named as the President.

[18] Roy and Mamata had a fall out in 2015 when his name came up in Saradha scam as well as in Narada sting operation in which TMC leaders are involved.