Russia left-back Yuri Zhirkov put the London club, beaten by Manchester United in the 2008 final after a penalty shootout at the same Luzhniki Stadium, ahead before French striker Nicolas Anelka doubled the lead just before the break.
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Zhirkov, familiar with the artificial pitch after spending five seasons with Spartak's bitter Moscow rivals CSKA, pounced on a loose ball in the 23rd minute and volleyed spectacularly into the top corner of the net from 20 metres.
Anelka, who wasted a good chance to make it 2-0 when he lost control of the ball with the goal at his mercy, made amends in the 43rd minute by racing through the defence before driving low past keeper Andriy Dykan.
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It was Anelka's 50th goal for Chelsea and Zhirkov's first since his move to Stamford Bridge in July 2009 as the English champions recorded their 50th win in 98 games in Europe's premier club competition.
Manager Carlo Ancelotti said his team were not affected by the ghosts of 2008.
"I don't think the players talked about the last defeat at this stadium," the Italian told a news conference.
"It was not an easy game for us. We scored two great goals. They tried to come back in the second half but we had good control for the rest of the game."
Ancelotti praised his goal-scorers and Chelsea keeper Petr Cech.
"Zhirkov scored a fantastic goal and he should be very happy tonight. Nicolas is a fantastic player who gives us a great presence in front of the goal and Petr Cech also had a great game," said the coach.
SCARED SPARTAK
Ancelotti's Spartak counterpart Valery Karpin said his young team were overwhelmed by Chelsea's reputation.
"I think we just got scared, as simple as that," said the former Russia international. "We played better in the second half but the first half was a disaster."
Chelsea, missing several key players including Didier Drogba and Frank Lampard, started cautiously but Zhirkov's stunning strike changed things.
Spartak, without Brazilian playmaker Alex because of a thigh injury, created the first real chance in the 13th minute but Dmitry Kombarov blasted over the bar from 12 metres.
The Russians relied on long-range efforts mainly through Ireland winger Aiden McGeady and Brazilian striker Welliton after the interval but Cech was rarely threatened.
Chelsea maintained their 100 percent record in the section with a third successive victory while Spartak remained on six points. Olympique Marseille were hosting Slovakia's Zilina in the other Group F match later on Tuesday.
