The hosts won the toss and opted to bat first at Perth Stadium, consigning Pakistan to the field in searing heat.
Warner padded up under pressure to score runs, with an emotional goodbye from the five-day game at the third Test in Sydney in front of his hometown fans his stated goal.
In the lead-up, former paceman Mitchell Johnson questioned whether Warner deserved a hero's farewell given his recent poor red-ball form and involvement in the 2018 ball-tampering scandal.
The 37-year-old Warner, in his 110th Test, responded in typical swashbuckling fashion, crashing 11 fours and one giant six in his 67-ball knock.
He took a confident single off his first ball in an opening over from Shaheen Shah Afridi that leaked 14 runs.
After living dangerously on a pitch offering bounce, he settled down to bring up a 37th half-century off just 41 balls with a boundary from Faheem Ashraf.
At the other end Khawaja, wearing a black armband in solidarity with the people of Gaza, was happy to play second fiddle, reaching the break on 37.
He had a massive let-off on 25 when dropped by Abdullah Shafique, who fumbled his catch off a mis-hit pull shot.
Pakistan have never won a Test series in Australia and have failed to win a Test in the country since 1995.
They were beaten by an innings in both matches in Australia four years ago, when Warner ominously scored 154 and 335 not out.
Australia made just one change from their last Test, against England in July, with spinner Nathan Lyon fit again and back in the side.
Pacemen Aamer Jamal and Khurram Shahzad made their debuts for Pakistan under new captain Shan Masood.
