Thanks to Khawaja's unbeaten century, Australia ended the opening day on 251/3.
Playing in the country of his birth, Khawaja followed his 97 in the drawn first Test at Rawalpindi with a crafty 160 in the first innings at Karachi.
Thanks to his unbeaten century, the visitors ended the opening day on 251/3 after winning the toss and opting to bat first. They had progressed to 360/6 at the time of writing this.
"I was born in Islamabad but my parents are from Karachi, so this one meant a lot," Khawaja told reporters after the first day’s play.
It was his third century in four Tests, following his twin hundreds in the fourth Ashes Test against England at SCG in January.
"It's hard to rate them all, for every test hundred is pretty special. I think the Sydney ones are probably up there as my favourites. This one, after last week getting 97, it has got to be up there."
Khawaja enjoys a massive fan following in Pakistan because of his roots in the country and the Karachi fans applauded the southpaw after his 11th Test ton.
"It was really nice. In Islamabad they did the same and chanted 'Khawaja'. Here too when I got the hundred.
"They are so supportive, I could not have asked for more. I love it."
(With Reuters inputs)