Burns and fit-again Khawaja were nearing centuries as the Caribbean tourists again struggled to make any impression after losing by an innings and 212 runs in the first Hobart Test.
At tea, the Australians were 193 for one with opener Burns on 83 and Khawaja on 84 in an unbroken 164-run stand for the second wicket.
So far in the series, Australia have amassed 776 runs for the loss of just five wickets as the home side looked to build another formidable first innings total.
Khawaja continued his rousing form this season after scoring 174 and 121 in the first two Tests against New Zealand last month.
Selectors ultimately decided to make the tough decision to drop Shaun Marsh to fit in Khawaja's return despite Marsh hitting his highest Test score of 182 against the Windies in Hobart.
There was little joy for the maligned Windies although they removed dangerous opener David Warner cheaply for 23 in the fifth over of the innings.
Warner crashed boundaries off Kemar Roach's first three balls before plundering 15 off his opening over.
But Warner was out three overs later when his attempted pull shot lobbed to Marlon Samuels in the covers.
Samuels took three grabs at the ball before taking the catch for a crucial wicket for the Windies, removing Warner for 23 off 12 balls.
The MCG has proved a frustrating Test venue for Warner who averages 25.12 in eight innings at the ground wih his highest score of 62.
Australia are favoured to win the showpiece Boxing Day Test and retain the Frank Worrell trophy against the struggling tourists.
The West Indies last won a Test in Australia almost 18 years ago.
The West Indies also had a setback before the match when legspinner Devendra Bishoo succumbed to a shoulder injury.
Bishoo, who had been in line for a return to the team, fell heavily while fielding during practice and was sent to hospital for scans on his left shoulder.
