Vaughan resisted over seven hours for his 105 from 333 balls to help England survive a torrid final day, just as they did in the drawn first Test in Galle.
The tourists, who resumed on 89 for two chasing a highly improbable 368 to win, finished on 285 for seven.
Muralitharan took four for 64 from 56 overs to follow his four wickets in the first innings. He finished with a match analysis of eight for 124.
Vaughan's painstaking hundred, which revived memories of Michael Atherton's 10-hour match-saving 185 against South Africa in 1995-96, was his 10th in Tests and the first since he took over the captaincy from Nasser Hussain in July.
England looked likely losers when Muralitharan trapped Andrew Flintoff (19) lbw -- the third time the off spinner has claimed the all rounder's wicket in four innings -- and had Vaughan snapped up at bat-pad to leave England 233 for seven with an hour and 20 minutes remaining.
But Chris Read and Gareth Batty, who was given a reprieve on two after gloving a catch to short leg, batted a further 20 minutes until the umpires started the final hour at 4:36pm.
Sri Lanka captain Hashan Tillakaratne, who had set bizarrely defensive fields throughout the day, took the new ball in the 122nd over but soon turned back to his spinners as a sickly Chaminda Vaas ran out of steam.
As the minutes ticked away, Sri Lanka's frustration was heightened by regular time-wasting interruptions from England's 12th man Matthew Hoggard.
Batty and Read held firm, doggedly defending during an unbroken 87-minute partnership.
Batty finished with 25 not out and Read, previously having a wretched series with the bat, scored the most valuable 18 runs of his career.
Earlier, Vaughan and Graham Thorpe (41) frustrated Sri Lanka with an 87-run stand from 231 balls after the early loss of Nasser Hussain, who was brilliantly pouched one-handed by wicketkeeper Kumar Sangakkara off Vaas in the day's first over.
But Sri Lanka broke through immediately after lunch, Muralitharan winning a controversial caught behind appeal to dismiss Thorpe, though television replays showed clear daylight between bat and ball.
Muralitharan had a series of bat-pad and lbw appeals turned down afterwards as tempers started to fray and Sangakkara was warned by umpire Darryl Harper for sledging.
Kumar Dharmasena eventually broke through, having Paul Collingwood (24) caught at slip as he tried to work the ball to leg to end a 92-minute 41-run stand.
England also narrowly escaped defeat in the first Test in Galle, finishing on 210 for nine when bad light stopped play. The third and final Test starts in Colombo on Thursday.
Scoreboard:
Sri Lanka first innings 382 (T.Dilshan 63, D.Fernando 51 not out; A.Giles 5-116)
England first innings 294 (G.Thorpe 57, M.Vaughan 52; M.Muralitharan 4-60, C.Vaas 4-77)
Sri Lanka second innings 279-7 declared (T.Dilshan 100, M.Jayawardene 52)
England second innings (overnight 89-2)
M.Trescothick c Jayawardene b Vaas 14
M.Vaughan c Dilshan b Muralitharan 105
M.Butcher st Sangakkara b Muralitharan 6
N.Hussain c Sangakkara b Vaas 17
G.Thorpe c Sangakkara b Muralitharan 41
P.Collingwood c Jayawardene b Dharmasena 24
A.Flintoff lbw b Muralitharan 19
C.Read not out 18
G.Batty not out 25
Extras (b-3 lb-8 nb-5) 16
Total (for seven wickets, 140 overs) 285
Fall of wickets: 1-24, 2-50, 3-90, 4-167, 5-208, 6-233, 7-239
Did not bat: J.Kirtley, A.Giles
Bowling:
Vaas 29-7-59-2 (nb-3),
Fernando 7-1-21-0,
Dharmasena 26-2-74-1 (nb-2),
Muralitharan 56-28-64-4,
Jayasuriya 17-2-45-0,
Tillakaratne 1-0-1-0,
Samaraweera 1-1-0-0,
Dilshan 3-1-10-0
Result: Match drawn
First Test: Galle, match drawn
Third Test: December 18-22, Colombo.
Photograph: Reuters
