The Blues were under pressure after a string of unconvincing displays in Group E, but first half strikes from Drogba and Ramires ensured the anxiety and tension was lifted early on.
Drogba doubled his tally in the 76th minute to secure his side's progression through to the knock-out stages, and a draw between Racing Genk and Bayer Leverkusen saw Chelsea top the group after one of their best performances of the season.
Frank Lampard missed a penalty at Newcastle at the weekend before being substituted before the hour mark and he was confined to the substitutes' bench alongside Fernando Torres and Florent Malouda as Andre Villas-Boas named a conservative side with Oriol Romeu employed in the all important holding role.
Chelsea, who have qualified from the group stage every year since the 2003-04 season, knew that they could not afford to lose against a Valencia side brimming with confidence and boasting the prolific Roberto Soldado in attack, and the hosts started with menacing intent.
Daniel Sturridge dispossessed Jordi Alba superbly on halfway before finding Drogba, who laid the ball off to the onrushing Juan Mata, and Diego Alves was forced to make the first save of the match as the Spaniard drove a low shot on target in just the third minute.
Seconds later, the hosts went in front: Sturridge found Mata with a raking diagonal pass out to the left byline, and his cut back found the opportunistic Drogba, who jinked inside Antonio Barragan and fired a low shot beyond Alves.
For all Chelsea's swaggering approach, they were very nearly caught out seconds after the opening goal as Sturridge was caught out as Alba latched on to a long ball from Tino Costa and rattled the near post with a rasping strike from an acute angle with Petr Cech comprehensively beaten.
Chelsea have taken the lead in each of their Champions League group stage matches this season but have had a propensity to squander early advantages, and Cech was forced into a magnificent save to his right as Valencia skipper David Albelda unleashed a piledriver from 25 yards.
The visitors enjoyed sustained periods of possession, but Chelsea were the more incisive and doubled their lead in the 22nd minute. Drogba produced an inspired run from deep inside his own half before sliding a through ball into the path of Ramires which Victor Ruiz really should have cleared, but the defender dallied crucially and the ebullient Ramires nipped in to score his fifth goal of the season.
It should have been three on the half hour mark as Sturridge again outstripped Alba down the Chelsea right and forced his way to the byline, but chose to shoot from a tight angle with Alves able to save with consummate ease when a cut back to the onrushing Ramires would have been the preferred option for every Chelsea supporter and an exasperated Villas-Boas.
Unai Emery cut a hugely agitated and frustrated figure in the second half, but did not make a change to his side until he hauled off the dangerous Alba with Aritz Aduriz joining the anonymous and outnumbered Soldado in attack.
Sturridge continued to wreak havoc down the Chelsea right, and he latched on to a brilliant pass from the excellent Oriol Romeu on the hour mark and drove to the byline before again opting to shoot from an acute angle with Mata screaming for the ball in the six-yard box.
Cech pulled off another stunning save to deny Sofiane Feghouli in the 64th minute as the midfielder surged forward and lashed a fierce drive towards the far corner of the net, but the Chelsea goalkeeper dived full length to his left to save.
Villas-Boas made what appeared to be an enforced change as Ramires was taken off and John Obi Mikel was introduced as a second holding midfielder, and the hosts continued to play on the break to good effect.
With his side under the cosh, Sturridge lumped a long ball upfield to Drogba who controlled the ball with an exquisite touch before powering past Rami as though he was not there, only to lose his composure and drag a tame shot wide of the far post.
But the third goal did arrive to effectively end the contest and put secure Chelsea's place in the last 16 as Mata slipped a sublime through ball into the path of the buoyant Drogba, who finished with consummate ease past Alves with a clinical strike to double his tally and send Stamford Bridge into raptures.
It was the blow which sunk Valencia, and the Spanish side's energy was entirely extinguished as Chelsea were left to bask in a celebratory atmosphere with Villas-Boas having alleviated some of the pressure on his tenure with a tactically impeccable showing from his side.