Second-half goals from Igor Denisov and Konstantin Zyrianov secured the Cup for the Russian outfit and, in truth, the margin of victory should have been much greater.
Despite standing on the verge of a historic quadruple, Walter Smith's men never looked likely of becoming the first Scottish side to win a European trophy for 25 years with a dogmatic, defensive showing, bereft of inspiration or guile.
Their last continental win came against Russian opposition, in the Cup Winners' Cup final of 1972 against Dynamo Moscow, but Rangers never looked likely to repeat the feat in their 19th European match of an epic campaign.
Instead, it was former Ibrox hero Dick Advocaat who celebrated at the full-time whistle at having reached another impressive landmark with his side, one year on from leading Zenit to their first ever Russian league title.
Over 30,000 fans from north of the border packed into the 47,000-capacity ground and, outside, another 100,000 turned the streets of Manchester blue.
The colour aptly reflected the mood of the Gers support just minutes into the match, as it became evident that the Glasgow club were in for a long night.
As early as the fourth minute, UEFA man of the match Andrei Arshavin was unlucky to hit the side netting after leaving Kirk Broadfoot for dead down the Zenit left flank.
A 30-yard free kick from Radek Sirl forced Neil Alexander into a save and Viktor Fayzulin headed over from Arshavin's cross.
For their part, Rangers crafted sporadic spells of possession, but their rigid 4-5-1 formation left lone frontman Jean-Claude Darcheville completely outmatched against the outstanding Ivica Krizanac and Roman Shirokov.
In the face of the Gers' negligible attacking threat, Zenit captain Anatoliy Tymoschuk enjoyed an abundance of time and space to mop up the occasional loose ball in front of his back four.
Further up field, Arshavin repeatedly linked up with the overlapping Radek to threaten Rangers and bring Fatih Tekke and Zirianov into the game, the former thwarted inside the area by a fine Kevin Thomson challenge.
Having survived further attempts on their goal, including a rasping long-range effort from Radek, Rangers finally carved out an opportunity of their own.
With three minutes remaining in the half, Roman Shirokov brought down Darcheville 20 yards from goal, but Thomson ploughed his free kick wastefully into the wall.
After surviving a late penalty scare, when Arshavin's cross was handled by Broadfoot, Swedish referee Peter Frojdfeldt brought the half to a close and Rangers escaped into the dressing room with their dreams of victory still intact.
The second period began with the Glasgow club pushing up and, in the 54th minute, the players in blue were denied a penalty of their own as Darcheville tested Zenit minder Vyacheslave Malafeev for the first time.
The keeper could only parry the former Nottingham Forest striker's effort to Gers captain Barry Ferguson, who claimed that his goalbound shot was handled by Denisov.
Shirokov then cleared off the line from Steven Whittaker, allowing Zenit to break through Arshavin, who rounded Alexander only for Sasa Papac to head off the line.
And it was the winger who was the architect of Zenit's 72nd-minute breakthrough, splitting the defence with a superb through ball for Denisov to slot home.
Rangers were crestfallen and Advocaat's men were unlucky not to double their advantage through Zyrianov, but his shot hit the post with Alexander beaten.
Over the remaining 15 minutes, Smith threw caution to the wind in search of an equaliser, bringing on Nacho Novo, Lee McCulloch and Kris Boyd.
And it was Novo who squandered a great chance to equalise in the first minute of stoppage time, ballooning his shot over the bar.
With seconds remaining, Zyrianov ensured the win for Zenit with a tap-in from close range.