Weatherald crunched 27 boundaries from 160 balls on his way to the best first-class total of his career to lift South Australia to 6/322 in reply to the Warriors’ total of 514.
Wicketkeeper/batsman Cameron Bancroft was the star of WA’s innings, producing an unbeaten 228 as the home side piled on the runs before declaring at lunch with three wickets in hand.
Bancroft's 513-minute, 351-ball innings featured 22 fours and three sixes and was well supported by skipper Mitch Marsh, who notched 95 from 110 balls.
Pacemen Joe Mennie (3/130) and Daniel Worrall (2/122) were the only Redbacks to claim multiple wickets in the opening innings.
Several spiders earned starts on a batter-friendly pitch at the WACA, including experienced pair Callum Ferguson (33) and Tom Cooper (34), but were unable to build meaningful partnerships with the in-form Weatherald.
Alex Carey (26*) and Mennie (21*) negotiated the final overs before stumps and will resume at the crease on Wednesday.
South Australia trail Western Australia by 192 with two days of play remaining.