He achieved the milestone with his famous "doosra" delivery in the second Test against Bangladesh here, forcing former captain Khaled Mashud (12) to hole out to Lasith Malinga at deep square-leg.
The landmark wicket sparked celebrations from the Sri Lankan players who mobbed their star bowler, completing the feat 13 years after his Test debut in Colombo against Australia.
It also made him the first bowler to pick up 50 wickets against every Test playing nation, cementing his status as the greatest player in Sri Lankan history.
He had conquered another peak in the previous game at Chittagong, his 100th Test, when he became the first bowler to take 1,000 international wickets.
But he still has a way to go to catch Warne, who has taken 659 Test wickets and vowed last month there would be no easing up in his schedule despite turning 37 this year.
Reaching the feat hasn't been plain sailing for Murali, who has been accused of chucking.
Suspicions about his action were whispered soon after his debut in 1993 and he has been taunted by Australian crowds since he was first no-balled during Sri Lanka's Boxing Day Test against Australia in 1995.
Since then he has been checked and cleared four times by experts at UWA, who carry out testing on behalf of the International Cricket Council.
The latest tests in February showed that even bowling at faster speeds, both Muralitharan's controversial "doosra" and his offbreak deliveries complied with the rules.
His average elbow extension while bowling the doosra at an average of 86.5 kph was 12.2 degrees, well within the 15 degrees allowed by the ICC under current rules. The average for his offbreak was 12.9 degrees at 95 kph.
But the taunts have continued, and his feelings became evident in Perth last month when he was photographed making a one-finger gesture to a spectator who had "no ball" written across his chest.
Warne's rivalry with Murali in the race to become the world's greatest ever wicket taker has also seen the two players in sledging matches, most recently last year when Warne suggested his rivals had benefited by taking "cheap" wickets.
The Australian said that his world record tallies of 659 career wickets and 87 in a calender year will not last long because other bowlers got a lot of wickets against weaker opponents.
Without naming Muralitharan, Warne said: "There's a lot more cricket being played these days and you have teams like Zimbabwe and Bangladesh in there, with some teams playing them a lot more (than others).
"I've never played a Test against Bangladesh and only one against Zimbabwe, but there are some teams out there that play them a lot.
"Some blokes bowl at one end all day against those sort of countries and take lots of wickets. I'm sure that whoever those people are, they might get the record."
Muralitharan, the son of a hill-country confectioner, has taken more wickets (89) against Test minnows Zimbabwe than any other nation, and his 600th Test wicket was his 50th against Bangladesh.
The Sri Lankan ace also has to catch up with Warne for the number of deliveries in Test cricket. The Australian has bowled more than 37,000 balls, some 4,000 more than Muralitharan.