West Indies was 74 without loss at stumps in fading light at Perth Stadium.
Labuschagne scored 204, his second double century, and was out to the last ball before lunch.
Smith reached 200 not out and Australia declared when Travis Head was out on 99 after playing on offspinner Kraigg Brathwaite, the tourist's most successful bowler with 2-65.
West Indies openers Brathwaite, 18 not out, and Tagenarine Chanderpaul, 47 not out, successfully negotiated 25 overs.
The debutant Chanderpaul, the son of batting great Shivnarine, faced some testing moments at the crease, and took a painful blow on the groin from fast bowler Josh Hazlewood.
Chanderpaul hit a boundary off his first ball in test cricket and hooked skipper Pat Cummins for a towering six over long leg as he dominated the stand under floodlight.
Australia started the day on 293-2 with Labuschagne on 154 and Smith on 59, and the West Indies desperate for a breakthrough in cloudy conditions conducive for swing bowling.
Instead, Labuschagne and Smith continued from where they left off overnight and stubbornly piled more misery on the tourists.
Labuschagne smashed fast bowler Jayden Seales through the covers for his 20th boundary to bring up his double century. Then he fell when he edged Brathwaite as wicketkeeper Joshua da Silva finally held onto a catch after dropping Labuschagne on 132 and 194. Labuschagne's previous double century was 215 in 2020 against New Zealand in Sydney. This time, he batted for 483 minutes and hit a six and 20 fours off 350 balls.
His dismissal ended the 251-run stand for the third wicket, the sixth highest for Australia in test history.
Australia went to lunch on 402-3 and middle session belonged to Smith. He equalled Don Bradman's 29 test centuries in his 88th test.
Smith pushed a single to reach his hundred before lunch. Only Ricky Ponting (41), Steve Waugh (32) and Matthew Hayden (30) have scored more hundreds for Australia.
During the course of his 435-minute innings, Smith reached 4,000 runs in 44 home tests averaging 65.98 — third behind Bradman (98.22) and West Indian Gary Sobers (66.8) for home tests.
Adopting a new batting stance that has been more than a year in making, Smith batted flawlessly in facing 311 balls and hitting 18 boundaries. Smith has ditched his trademark back and across shuffle and stands tall and balanced at the crease.
Smith's other three double centuries were against England including his career-best 239 at the old WACA in 2017.
With the pitch quickening and the West Indies bowlers tiring, Smith and Head put the tourists to sword in a run-a-minute 196-run fourth-wicket stand. The pair went on a leather hunt in smashing 166 runs in less than 30 overs.
A ball after Smith's fourth double century, Head on 99 played on and missed out on a deserved century. He hit 11 fours off 95 balls during his 160-minute stay with Smith.