Dual-registered Gloucester flanker Dan Thomas scored on his Rotherham Titans debut but the sending off of Ben Foley at the start of the second-half ensured there was no happy returns to Old Deer Park for Justin Burnell.
Burnell led London Welsh to the Premiership earlier this decade, and took charge of Rotherham towards the end of last season to stave off the threat of relegation.
Two wins from their first six matches to start this season’s Championship campaign had left them languishing in 10th.
But a victory over South Yorkshire rivals Doncaster Knights last week was the perfect start to their B&I Cup campaign.
However, after leading 15-7 at the break at Old Deer Park, they were undone by the rampant Cup holders in the second period.
The visitors led thanks to tries from Foley and Thomas, one of six players the Clifton Lane club have signed on a dual-registration deal from Premiership side Gloucester.
Thomas is a 23-year-old former Llanelli and Wales Under-20 captain.
The home side’s sole reply in the first half came through Koree Britton, but Foley’s dismissal in the 41st minute for a tip-tackle on Welsh’s James Lewis, turned the tide and the Exiles took full advantage.
Lewis crossed twice with Ryan Glynn, Adam Kwasnicki and Seb Jewell also scoring as the Exiles ran out comfortable winners to take control of Pool 2.
Lloyd Evans added three penalties in the second half to the one he scored in the first, but the 14 men of Rotherham were always going to struggle to contain their adventurous hosts.
Doncaster’s game with Munster A in Pool 2 was postponed in respect of the death of Munster head coach Anthony Foley.
Russian side Enisei-STM claimed a second British scalp in eight days, with a bonus-point 38-18 home win over Newport Gwent Dragons in the European Rugby Challenge Cup.
Enisei-STM last Saturday defeated Worcester Warriors 19-12, but this win takes them top of Pool Three at least until the next round in December.