Axed Victorian Test batsman Peter Handscomb compiled an unbeaten century to put the hosts in charge of the clash with South Australia.
Handscomb notched his 14th first-class century at the MCG to lift the Vics to 7-345 at stumps holding a 101-run first-innings lead.
His innings swung the contest back in his side's favour after SA enjoyed a bright period just before lunch and throughout the middle session.
Victoria resumed at 0-72 in reply to South Australia's first-innings total of 244, with Travis Dean and Marcus Harris moving the score along to 132 in the morning session.
After his unbeaten 250 against NSW last week, Test hopeful Harris made it 315 runs without dismissal before he was caught behind off the bowling of Nick Winter for 65.
Winter also removed Dean for 75 from 133, then had Cameron White caught behind for a duck for two wickets in three balls and finished the pick of the bowlers with figures of 3-81 off 28 overs.
Allrounder Cameron Valente also contributed with two wickets in the middle session as part of a marathon spell of 13 consecutive overs.
Victorian captain Handscomb was forced to dig in and patiently see out the storm after the Vics fell to 5-193.
On a pitch that still offered a bit for bowlers, the 27-year-old was solid in reaching 103 off 186 balls, with 11 fours, after tea then saw out a tricky period before stumps.
He will resume on 123 on day three with Test seamer Peter Siddle on 13.