City's international players made the difference with Wales captain Jess Fishlock and Matildas striker Larissa Crummer both netting two goals.
American Ashley Latch and Australian international fullback Steph Catley provided two assists each in a powerhouse performance from a City side hunting a third successive championship.
Newcastle defied the run of play to take a 2-1 first-half lead at AAMI Park thanks to a quickfire double from striker Katie Stengel, but they had no answer as City scored four unanswered second-half goals.
City crashed to a 4-1 defeat in their season opener against Perth Glory a fortnight ago, and then needed a late goal to secure a derby win over last season's cellar dwellers Melbourne Victory.
However, the champions dominated possession for long periods and never looked like losing after Crummer drew the two sides level on the stroke of halftime.
There was good news also for Canberra United who scored twice in the final quarter-hour to earn a dramatic 3-2 come-from-behind win over Sydney FC.
Prolific striker Michelle Heyman continued her successful return from long-term injury with a double, including the winner scored six minutes from time.
It completed an impressive comeback for the team for the nation's capital after Toni Pressley equalised, following two penalties converted by Sky Blues' midfielder Kylie Ledbrook.
It was a first win for new coach Heather Garriock in the team's second outing, while two-time champions Sydney FC remain bottom after three successive defeats.
Meanwhile, Perth Glory firmly felt the absence of Sam Kerr with the West Australians falling 3-1 to unfashionable Adelaide United on Friday.
American Makenzy Doniak netted a sparkling hat-trick to knock over a Glory side who had won two from two, scoring eight goals in the process.
Perth could be without Kerr for several weeks after Matildas' superstar missed the match with a quad injury.
Also on Friday, Brisbane Roar edged past Western Sydney Wanderers thanks to a lone strike from Carson Pickett.