The pair's composed 79-run stand tempered the West Indies' cheer after their bowlers took early wickets in the wake of some doughty tail-end batting at the Melbourne Cricket Ground.
After Khawaja's dismissal for 56, captain Smith and Mitchell Marsh guided Australia to 179 for three at stumps in glorious sunshine. Smith was unbeaten on 70 with all-rounder Marsh on 18.
Thrashed within three days in the opener in Hobart, West Indies were left on the brink of losing the series 2-0 with a game in hand.
But anchored by half-centuries to debutant paceman Carlos Brathwaite and Darren Bravo, the tourists took heart from frustrating Australia's bowlers for two sessions.
Replying to Australia's mammoth first innings declaration at 551-3, West Indies resumed in the morning on 91-6 and eked 180 runs from their last four wickets to be bowled out for 271 on the stroke of tea.
Brathwaite rode his luck to make a rousing 59, with Bravo building stubborn partnerships with the tail-enders during a patient 81.
MONUMENTAL EFFORT
"From the team's point of view, I was happy with the fight that we showed," Brathwaite told reporters.
"Ultimately, the game is still very, very far out of our hands and it will take a monumental effort to bring ourselves back into the game... But that's a challenge we look at tomorrow.
Although trailing by 280 runs, the West Indies bowlers attacked with renewed purpose and captain Jason Holder had opener Joe Burns caught in the slips for four.
After engaging in some heated banter with opener David Warner, Holder caught the pint-sized vice captain for 17 in the gully to give Brathwaite his first test wicket and reduce the Australians to 46-2.
Brathwaite's exuberant celebration bowled his captain over but Khawaja, one of four first innings centurions for Australia, teamed up with Smith to put down the minor insurrection before he was caught behind attempting an audacious ramp shot.
It was a memorable day for Brathwaite, who was dismissed twice by paceman James Pattinson but reprieved by the television umpire.
He was bowled attempting an ugly heave on 13, then caught hooking to long leg for 50, but was called back twice when replays showed the bowler had over-stepped the crease.
"It cost us a bit of time today and a few runs," a red-faced Pattinson told reporters after finishing with four wickets along with spinner Nathan Lyon.
"It's something that I've got to change."
(Editing by Amlan Chakraborty/John O'Brien)
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