The 36-year-old veteran, whose longevity is partly due to having not played international white-ball cricket since 2019, reached the milestone in his 123rd match.
He began the first Test in Perth on 496 wickets and was left stranded on 499 after Pakistan's first innings. But he finally reached 500 on day four by dismissing Ashraf lbw on review, with his teammates mobbing him in celebration.
Lyon then bowled Aamer Jamal in the same over for his 501st.
Affectionately known as "Garry" after former Australian Rules Football player Garry Lyon, he made his debut in 2011 and has best figures of 8-50, collecting 23 five-wicket hauls and 10 wickets four times so far.
He told reporters before the Perth match that he wanted to continue playing at international level until Australia's next Ashes sojourn to England in 2027.
But Lyon would not say how many more wickets he felt he could get.
"I'm not putting a number on it," he said. "I want to play cricket for as long as I can.
"I'm feeling really confident, really happy with where everything is at and it's just about going out there and performing now."
Lyon still has a long way to go to match the exploits of fellow spin kings Muttiah Muralitharan (800) of Sri Lanka and Australia's Shane Warne (708), who head the all-time list.
A classical spinner who flights the ball, the right-armer could feasibly catch West Indian great Courtney Walsh (519) during the current three-Test series.
If not, the milestone should be in sight during Australia's two-Test home showdown with the West Indies that follows later in January.
After that, fellow Australian Glenn McGrath on 563 would be his next target.
English pair Jimmy Anderson (690) and Stuart Broad (604), along with India's Anil Kumble (619) fill out the 500-club.
Long-time teammate Steve Smith praised Lyon as a hugely important member of the side.
"What he brings to the attack and the control and different tempos - he can play defensive roles, he can play an attacking role and he's got all the tricks," he said ahead of the Test.
"He's been incredible, particularly the last three or four years.
"He's continually learning and trying to get better as well. He's a valuable - if not the most valuable member in this team for our attack."
