Lorenzo Insigne's stunning 40-yard strike had the travelling hordes in dream land after just eight minutes of the last 16 first leg.
However, Benzema soon headed home an equaliser before Kroos and Casemiro fired home from outside the box early in the second half to give the holders a commanding lead ahead of the second leg on March 7th.
“We played a great game, above all at the start,” said Madrid boss Zinedine Zidane.
“The shame was to concede given the start we made, but we equalised quickly to get back in the game and in the end it is a logical result.”
Napoli coach Maurizio Sarri lamented his side's slackness in possession, but believes they still have a chance back at the San Paolo given it had taken what he considered Real's best performance in three months to beat them.
“Clearly Madrid played their best game of the past three months and we didn't play our best,” said Sarri.
“If we manage to play at our best we are not that far away. We may lose (in the second leg) but we can go for it.”
With former Napoli great Diego Maradona watching on, the atmosphere reached fever pitch before kick-off as up to 10,000 travelling fans were estimated to have made the trip from Naples for only their side's second ever appearance in the last 16.
By contrast, Real are in the knockout stages for the 20th straight season and it was the home fans who nearly had something to cheer inside 30 seconds as Benzema's shot from close range was parried by Pepe Reina.
However, it was Napoli who got off to the perfect start just eight minutes in when Insigne took aim from 40 yards and caught Madrid 'keeper Keylor Navas out of position with a superb effort that curled around the Costa Rica international.
Madrid, though, showed the response of champions to level just 10 minutes later when Dani Carvajal's cross with the outside of his right boot picked out Benzema to power home a header from close range.
Cristiano Ronaldo should have had one of the two goals he needs to reach 100 in European competition on 27 minutes when great work from Benzema and Luka Modric freed the World Player of the Year inside the area, but he blasted well over the bar.
Madrid's control of the first 45 minutes grew as the half went on and only a combination of Reina and the post denied the hosts a lead at the break.
This time Ronaldo was inch-perfect with his low cross for Benzema, but his effort was tipped onto the woodwork and behind by Reina.
The tie did swing decisively in Madrid's favour within 10 minutes of the restart however.
Firstly, Ronaldo played provider once more with a fine run down the right and measured cut-back for Kroos to slot home from the edge of the box.
Then Napoli were struck by a thunderbolt from the most unlikely source as defensive midfielder Casemiro pounced on a looping clearance to volley first-time past a helpless Reina.
Napoli had the chances to set up a thrilling return leg as Dries Mertens, who had scored 14 goals in his previous 11 appearances, fired over with the goal at his mercy from former Madrid winger Jose Maria Callejon's fine lay-off.
Mertens also saw another effort smothered by Navas from close range and Callejon a goal ruled out for offside as Napoli slumped to their first defeat in 19 games.
By AFP's Kieran Canning