Danny Welbeck netted a brilliant brace on his first Arsenal start since May before Theo Walcott's hat-trick offered further cheer for suspended manager Arsene Wenger, who watched a rampant 5-0 thrashing of Southampton from the St Mary's stands.
Claude Puel's Saints were excellent in overcoming Liverpool to reach the EFL Cup final in midweek but a much-changed XI did not find the fourth round of the FA Cup to be such forgiving terrain.
Walcott then took centre stage, having missed the past six matches with a calf problem, and ensured Wenger's behaviour could be far more measured than the touchline fury from last weekend's win over Burnley that landed him with a four-game ban from the dugout.
The man who would depart with the matchball found space down the right against his former club in the third minute and the England winger's cutback reached Jeff Reine-Adelaide, whose shot was deflected behind.
Having had little trouble relocating his match sharpness, Welbeck looked to make hay and it was 2-0 when he immaculately controlled Alex Oxlade-Chamberlain's lofted pass and slotted left-footed through Lewis' legs.
Hojbjerg also sent a free-kick into the side-netting but had an unwitting role in Arsenal's third as Jack Stephens unceremoniously thumped a clearance into his face.
Welbeck retrieved the ball and exchanged passes with Lucas before lacklustre defending from Sam McQueen made Walcott's finish more routine than it might have been.
Lewis held a shot from rampaging full-back Hector Bellerin as Arsenal's pressure and total dominance began after the interval.
Southampton's weary defence would not have been heartened by the sight of Alexis Sanchez ready to replace Welbeck in the 65th minute. Four minutes later the Chile superstar hit the byline and pulled the ball back for Walcott to sidefoot his second.
