Andrea Stramaccioni's young side saw lots of the ball but lacked quality in the final third as the Russians' treble of finishes sees them progress as champions of the group.
Karadeniz Gokdeniz's second-minute strike, which came about courtesy of a defensive mistake, and Salomon Rondon's pair of finishes in the latter stages highlighted the gulf in experience between the two teams in Russia.
With qualification already wrapped up, Andrea Stramaccioni opted to field a youthful XI for the trip to the Tsentralnyi Stadion, handing the likes of Andrea Romano, Marco Benassi and Isaac Donkor their Nerazzurri debuts.
It was one of their first-team stars that was guilty of gifting Rubin their first goal, though. In just the second minute, Alan Kasaev's cross was guided onto the post by Juan Jesus, allowing Karadeniz to tap home the rebound.
Philippe Coutinho was given another chance to stake his place in the Inter side, but he failed to piece together an opening for the visitors in the first half, while Marko Livaja again failed to prove his credentials as an able deputy for Diego Milito.
A scrappy initial period soon came to an end, with little in terms of enterprise being demonstrated by either outfit, and Stramaccioni threw on captain Javier Zanetti and European goal hero Rodrigo Palacio in an attempt to shake things up.
It looked like an inspired pair of substitutions as Inter began to take control of the match, as the Argentine forward interchanged with Andrea Ranocchia in a probe towards the Rubin box, but he saw his lot shot cannon off the post.
Unfortunately for the Italians, the hosts had an ace of their own up their sleeves in Rondon. Berbas Natcho's hooked pass over the Inter defense was latched onto by the former Malaga striker, and he outmuscled Donkor to net to make it 2-0.
Rubin Kazan finished off Inter, as Karadeniz drifted into the box from the right-hand side and drilled in a low cross for Rondon to tuck home from a matter of yards out.
The result leaves Rubin top of Group H and three points clear of the Serie A giant with one round of matches remaining, but the superior head-to-head record means the Russians progress as leaders of the pool.