Yuri Zhirkov scored his first goal for Chelsea - a spectacular long-range volley - to get Carlo Ancelotti's side on their way in Russia and Nicolas Anelka added a second before half-time to make sure of the win.
Victory over the Moscow side at Stamford Bridge in a fortnight's time will guarantee the Premier League champions a first-place finish in the group.
The Blues, who lost on penalties to Manchester United in a heartbreaking final at the Luzhniki Stadium two years ago, returned in style to kill off the challenge from the group's only other unbeaten side.
Chelsea had plenty of possession in the opening exchanges but it was Spartak who engineered the first opportunity of the game in the 11th minute.
A superb run through the heart by Sergei Parshivlyuk saw him supply a perfect pass to the unmarked Dmitri Kombarov but the Spartak winger sent his left-foot shot high over the bar from the edge of the penalty area.
Petr Cech saved his side in the 14th minute when an outstretched right leg prevented Welliton's volley from sneaking in at the near post but Chelsea's response was immediate with Florent Malouda on shooting just wide of Andriy Dykan's left-hand upright from the edge of the area.
And the Londoners went in front in the 23rd minute when John Obi Mikel's long ball was knocked into the path of Zhirkov, who fired a 25-yard volley into the roof of the net.
It was Zhirkov's first goal for the Blues and arrived just hours after the former CSKA Moscow man had pledged to live up to his £18million price tag.
Michael Essien had the chance to make it two for the Blues in the 31st minute but he elected to cross the ball instead of shooting from an acute angle.
Anelka then whipped the ball off the toes of Marek Suchy but his attempted cross was deflected for a corner which Chelsea failed to capitalise on.
Anelka squandered another chance in the 37th minute when he latched onto a poor pass and ran clear of the Spartak defence only to over-run the ball and allow Dykan to smother.
However, Anelka made up for his mistake with a second goal for the Blues in the 43rd minute.
The France striker collected the ball after a driving run by Essien and then turned inside a Spartak defender before placing a low shot under Dykan to score his 50th goal for the club.
Spartak began the second half in much brighter fashion but Ari sent the ball high over the bar from the edge of the penalty area with their first effort in the 47th minute.
In the 48th minute, Aiden McGeady, who had been relatively quiet in the opening half, forced a corner for the home side with a dangerous 20-yard drive.
Cech dealt with another McGeady effort easily as the Blues coped with the Spartak onslaught but he was forced into another save from Kombarov in the 59th minute as the home side continued to search for a way back into the game.
Ibson thought he had reduced the deficit for Spartak in the 63rd minute but his shot was tipped over by Cech who then kept out another effort from the same player moments later.
Chelsea were under serious pressure but John Terry, who missed the crucial penalty two years ago, was in outstanding form at the back to keep the Russians at bay.
Essien shot wide from 10 yards when a goal seemed certain in the 72nd minute but Spartak continued to drive forward and Cech dived low to claim a long-range effort from Ari in the 81st minute.
However, Chelsea held on to maintain their perfect record in Europe this season.