Jayawardene struck three successive boundaries off paceman Shanthakumaran Sreesanth to end the contest with more than one over to spare.
His efforts overshadowed a fine century from Suresh Raina, who struck 106 to rescue India from a top-order collapse as they were bowled out for 245.
Kumar Sangakkara had put Sri Lanka in a strong position with his fourth half-century in five matches. Sangakkara, who hit 55, shared a second-wicket stand of 93 with Tillakaratne Dilshan, who made 49.
Man of the match Nuwan Kulasekara (four for 48) and his new-ball partner Chanaka Welegedara (three for 53) had earlier run through India’s top-order after Sangakkara won his fifth straight toss and opted to field first.
India slumped to 60 for five before a 106-run partnership between Raina and Ravindra Jadeja (38) steadied the ship.
Scoreboard
India innings
V. Sehwag c Sangakkara b Kulasekara 42
G. Gambhir b Kulasekara 0
V. Kohli c Sangakkara b Welegedara 2
Y. Singh c Samaraweera b Welegedara 0
M. Dhoni c Sangakkara b Kulasekara 14
S. Raina b Welegedara 106
R. Jadeja lbw b Dilshan 38
H. Singh lbw b Randiv 11
Z. Khan c Samaraweera b Kulasekara 16
A. Nehra not out 2
S. Sreesanth b Perera 4
Extras (lb-4 w-6) 10
Total (all out; 48.2 overs) 245
Fall of wickets: 1-1 2-4 3-16 4-47 5-60 6-166 7-213 8-233 9-237
Bowling: Kulasekara 10-0-48-4 (w-1), Welegedara 10-1-53-3, Thushara 6-1-26-0 (w-2), Randiv 9-0-47-1(w-1), Perera 8.2-0-49-1(w-1), Dilshan 5-0-18-1(w-1)
Sri Lanka innings
U. Tharanga c Kohli b Nehra 0
T. Dilshan c Dhoni b Yuvraj 49
K. Sangakkara c Sehwag b Harbhajan 55
M. Jayawardene not out 71
T. Samaraweera b Jadeja 27
T. Kandamby lbw b Harbhajan 18
S. Randiv run out 17
T. Perera not out 6
Extras (lb-1, w-4 nb-1) 6
Total ( six wickets; 48.3 overs) 249
Fall of wickets: 1-0 2-93 3-109 4-157 5-189 6-228
Bowling: Nehra 1.2-0-2-1 (nb-1), Sreesanth 9.3-0-72-0, Kohli 1.4-0-12-0, Zaheer 10-0-51-0(w-2), Harbhajan 10-0-41-2 (w-2), Yuvraj 9-0-41-1, Jadeja 7-0-29-1