Pakistan started briskly but lost their way against the spinners in the middle overs and Perera then returned with the ball to take three wickets for 19 runs and mop up the lower order as the tourists were all out for 233 in the 44th over.
In-form Mathews, who also scored 89 in a losing cause in the first ODI at the same venue at Hambantota, and Perera added 87 for the seventh wicket as Sri Lanka added 80 in their last six overs to set Pakistan a steep target.
Mahela Jayawardene (67), who has retired from both tests and twenty20 internationals, propped his team up with a 122-run stand with Mathews for the fourth wicket after Sri Lanka were reduced to 62 for three.
Part-time off-spinner Mohammad Hafeez pegged Sri Lanka back with a three-wicket burst as the hosts were reduced from 184-3 to 194-6 in the space of a few overs.
Mathews consolidated again before falling to left-arm paceman Wahab Riaz, who was the most successful bowler with four for 65, but by then the hosts had closed in on the 300-run mark, which was breached by Perera's pyrotechnics.
Hafeez (62) and opener Ahmed Shehzad (56) added 96 for the second wicket in quick time for Pakistan but both fell to leg spinner Seekkuge Prasanna, who was brought into the Sri Lanka team for the second match.
The required run-rate kept creeping up and left-arm spinner Rangana Herath piled on the pressure by taking out Pakistan captain Misbah-ul-Haq (36) and Sohaib Maqsood (nine) during the batting powerplay.
Big-hitting Shahid Afridi (17) tore into Lasith Malinga in an over, hitting the paceman for three fours, but did not last long as Perera got into the act.
Fawad Alam (30) ran out of partners and became man-of-the-match Perera's third victim before Malinga came back to clean up Junaid Khan for his second wicket and complete the victory.
The third and final match of the series will be played at Dambulla on Saturday.
(Writing by Sudipto Ganguly in Mumbai; editing by Justin Palmer)
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