After the victory in the inaugural Women's Champions Cup on February 1, Arsenal dominated from the start in Belgium on Wednesday night to close in on a last-eight meeting against London rivals Chelsea.
Frida Maanum led the visitors with two goals and Olivia Smith showed she was worth the record transfer fee Arsenal paid Liverpool for her in July. Also, Kim Little came on as substitute to play her 400th game for the Gunners.
Caitlin Foord set up two goals, Matildas teammate Kyra Cooney-Cross entered the match on 73 minutes while another Australian in defender Steph Catley remained on the bench.
Maanum headed in the opener after meeting a cross by Foord from the right in the 22nd minute.
Smith doubled the advantage a quarter of an hour later with a clinical finish as the Canada forward found the far corner of the net with a first-time low shot.
Maanum was left unmarked in the box to add her second, with Foord setting her up again early in the second half before substitute Alessia Russo completed the rout with her fifth of the campaign.
The revamped format has followed the men's competition with an opening league phase of six rounds instead of eight.
The top four in the standings — Barcelona, Lyon, Chelsea and Bayern — advanced directly to the quarters. Teams placed fifth to 12th went to the playoffs round.
Arsenal finished the league phase in fifth while Leuven were 12th in their first campaign in Europe's top competition.
The two met in the 18-team league phase with Arsenal winning 3-0 away.
With AAP.