The Scotsman was presented with a cake in a stadium ceremony Tuesday after he became the ninth active man to win 500 matches by beating Kevin Anderson 6-4, 3-6, 6-3 at the Miami Open.
Murray, who improved to 500-155, is the 46th man to reach the milestone during the Open Era, and the first from Britain.
"I don't know why, but getting to 500 gives me motivation to go on and try and win more," Murray said. "I hope I've still got a lot more wins in me."
The No. 3-seeded Murray, who won the Key Biscayne title in 2009 and 2013, next plays unseeded Dominic Thiem of Austria, who beat No. 28 Adrian Mannarino 7-6 (5), 4-6, 7-5.
No. 8 Tomas Berdych advanced when No. 17 Gael Monfils fell and hurt his hip. Berdych was leading 6-3, 3-2 when Monfils retired.
Monfils, seeded 17th, said he bruised his hip but hopes to be able to play in his next scheduled tournament in Houston.
Next up for Berdych is unseeded Juan Monaco of Argentina, who beat No. 29 Fernandez Verdasco 6-3, 6-3. Verdasco was coming off an upset win over Rafael Nadal.
No. 6 David Ferrer beat No. 12 Gilles Simon 7-6 (5), 6-0. Ferrer will face the winner of the match between four-time champion Novak Djokovic and Alexandr Dolgopolov.
In women's play, No. 9 Andrea Petkovic became the first semifinalist when she beat No. 14 Karolina Pliskova 6-4, 6-2.
To beat the 6-foot-8 Anderson, Murray relied on lots of defence and just enough offence. He scrambled all over the court to keep points going, and in the final game made improbable saves to extend rallies on consecutive points, winning both.
When Murray broke for a 3-1 lead in the final set, he screamed "Come on!" loud enough to startle any sunbathers across the street on Crandon Beach. He easily held from there, winning 12 of 13 points in his final three service games.
"In the third set I created quite a lot of chances, and served better as well," Murray said.
While Anderson had the bigger serve, Murray lost only eight points on his first serve.