Karunaratne, Oshada Fernando fifties ensure series ends at 0-0 after both Tests ended up drawn.
Brathwaite, Mayers, Holder of half-centuries helped West Indies reach 280 for 4 before declaring late on day four with a 376-run lead.
Only 42.1 overs played in the third day, they reduced visitors to 250 for 8 at stump before rain returned.
Suranga Lakmal took 4-94 but the Brathwaite century and Cornwall 73 kept the home team strong.
Every Sri Lankan bowler took a wicket, with Lakmal leading the way with three end day one of the second Test on equal footing.
It will be all to play for in the second Test after a resolute performance from the West Indies batting order held off Sri Lanka on day five.
The West Indies are up against it in the first Test, chasing a huge target after another good day with the bat for Sri Lanka.
The pair put on 162 for the third wicket after the hosts picked up a 102-run lead.
Rahkeem Cornwall blasted a maiden Test half-century and dominated an eighth-wicket partnership of 90 with Joshua da Silva to lift the West Indies to 268 for 8.
Kemar Roach picked up three as Sri Lanka collapse to 169 despite Lahiru Thirimanne fifty.
