Group K always looked like it would be a cakewalk for Spurs, who came through their toughest test 2-0 victors thanks to Defoe and Nacer Chadli strikes in the first half on the outskirts of Moscow.
It was an impressively comfortable performance from Andre Villas-Boas' heavily rotated side, which was still awash with star quality unlike the hosts.
Anzhi's big-spending was brought to an abrupt halt in the summer, leading to a dramatic fire sale that meant there were only three survivors from the side that started March's last-16 clash at Newcastle in Thursday night's line-up.
Such changes have seen the Russian side fail to collect a single win this season - a run that looked certain to continue when Defoe clinically fired Spurs ahead after 34 minutes.
The hardy 150 travelling fans were celebrating once again five minutes later, with Kyle Walker collecting a Lewis Holtby pass and squaring for Nacer Chadli to sweep home.
Anzhi returned for the second-half rejuvenated but Spurs held firm, as their run without conceding in this year's competition stretched to a fourth match.
The result was not surprising given the way 'The Anzhi Project' has spectacularly unravelled in recent months.
Billionaire owner Suleyman Kerimov significantly withdrew his backing in August, leading the likes of Samuel Eto'o, Willian and Lassana Diarra to head for pastures new.
If that was not bad enough, Anzhi have been forced to play European matches away from Makhachkala due to the current conflict in Dagestan.
Source: PA
Source: PA