Bowlers shine as Australia take control to lead Pakistan by 300 on day three
Off-spinner Lyon sits on 499 test wickets after claiming 3-66 while Imam-ul-Haq top-scored with 62 for the visitors, who were bowled out in 101.5 overs.
Opting not to enforce the follow-on, Australia ended the day on 84-2 from 33 overs having posted 487 in their first innings.
"I think batting looked really tough there at the end. As the game goes along I think the cracks will come more into play," Australia paceman Josh Hazlewood, who picked up 1-49, told reporters.
Resuming on 132-2, Pakistan almost lost Khurram Shahzad to a run-out on the first ball of the day but skipper Pat Cummins (2-35) ensured no further damage was done, clean-bowling the nightwatchman (7) two deliveries later.
Imam, who uncharacteristically danced past a Lyon delivery to get stumped by Alex Carey, had consolidated with Pakistan's premier batsman Babar Azam (21) but a collapse before lunch saw the tourists lose three quick wickets for 14 runs.
Some resistance from Agha Salman (28 not out) propped up Pakistan but when Aamer Jamal (10) gave Lyon his second stumping for wicket 499 the modest crowd of 15,956 came alive, anxious to witness the impending milestone moment.
Part-time spinner Travis Head, losing all sense of occasion, ended the Pakistan innings when he drew tail-ender Shaheen Afridi into a slog-sweep which found Usman Khawaja at mid-on.
"Travis said, when they replay your 500th wicket you don't want it to be a tail-ender, you want it to be a good wicket up the top," Hazlewood said joking.
To start the post-tea session, Australia lost first innings centurion David Warner for a duck and Marnus Labuschagne for two as Shahzad's double strike threatened to inject some spice into the contest.
Pacers Shahzad and Afridi showed a better understanding of the Perth Stadium conditions in their second effort, aided by a slight deterioration of the surface, bowling with aggression to restrict the hosts to seven runs in the first 10 overs.
Khawaja and Steve Smith slowly steadied the ship, but not without a late scare when Smith hooked Afridi just over the head of deep fine leg for six, to see their side through to the close with an unbeaten 34 and 43 respectively.