Manchester City power into Champions League knockout stages with Moscow victory
The result never seemed in doubt after Aguero hit his first from the penalty in the third minute at the Etihad Stadium and the in-form hosts were 3-0 up after an hour.
Seydou Doumbia twice disrupted City's flow with a goal on the stroke of half-time and a 71st-minute penalty but Manuel Pellegrini's men were not threatened and secured qualification for the first time with two games to spare.
Aguero's second after 20 minutes was his 13th of the season and Negredo then put City in complete control. He added his second soon after the break and completed his treble in the last minute. After exits at the group stages in each of the past two seasons the result represented the next major step forward in City's development.
After the meeting between the two clubs in the Russian capital a fortnight ago was soured by racist chanting aimed at Yaya Toure, there was also focus on the crowd.
Stewards also acted quickly to remove a banner unfurled by City fans reading, 'Free Pussy Riot', referring to the members of the imprisoned members of the Russian protest band.
Midway through the first half police and stewards also moved in among the CSKA supporters after what may have been a minor disturance and a smoke bomb was later let off.
On the field City were quickly into their stride as the same side that started Saturday's 7-0 win over Norwich picked up where they left off.
Aguero clinically dispatched the penalty to move clear of Francis Lee as City's record goalscorer in Europe.
City began to assert themselves more as Toure shot over from a free-kick and Silva combined with Samir Nasri before lashing into the side-netting.
Negredo volleyed over from a poor clearance and Toure curled a long-range effort just wide as the pressure continued.
Negredo claimed the third on the half-hour as he found Aguero wide and then received a perfect return pass into his path from the Argentinian to tap in from six yards.
An Aguero overhead kick was blocked and Negredo narrowly failed to turn in another good cross from his strike partner.
CSKA broke the procession on the stroke of half-time as Pontus Wernbloom split the City defence with a superb through-ball and Doumbia glided around Pantilimon to pull one back.
It may have raised more questions over the defence but they could wait for another day as City resumed normal service in the second half.
Nasri met a Toure long ball with a superb first-time pass that gifted Negredo another tap-in.
Toure's Ivory Coast team-mate got up to send Pantilimon the wrong way from the spot and reduce the arrears.
It was almost immediately cancelled out as Negredo narrowly failed to claim his hat-trick with a shot that flew inches over the bar.
The Spaniard went close again after substitute Jesus Navas caused more defensive uncertainty but his close-range effort was deflected wide.
City grabbed the fifth goal their superiority deserved as Negredo wrapped up the scoring in injury time by heading home a cross from James Milner to complete his hat-trick.