Zico Zoremsanga scored on either side of half-time and a second half injury time strike from F Lalrinpuia helped the north eastern state to romp home in style.
Railways - who had not won the Santosh Trophy since 1966 - came closest in the 43th minute when Rajesh S's close-range header came off the horizontal.
Courtesy their triumph, Mizoram bagged a purse of Rs 5 lakh while runners-up Railways got richer by Rs 3 lakh.
The match started at a good pace with both the outfits looking for an early goal.
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With Railways missing their first choice centre-backs Vimal Kumar and Rajiv Boro due to suspension, Mizoram looked to take advantage but first-timer Akhil Rajbanshi and makeshift stopper-back Dipankar Das stood firm.
David Larinmuana found Lalnumawia free on the left with a good-looking ball from midfield but the latter was well marked by Dipankar and right-back Y Raju Singh.
It was end to end stuff with the action mostly concentrated in the final third. The match's best chance fell to Railways when striker Rajesh S hit the bar from close. Kisku tried his luck from the rebound but his effort was blocked.