The champions recovered from a chaotic 3-3 draw at home against Parma with a straightforward victory and a more composed performance at MAPEI Stadium on Sunday.
Khedira scored his second goal of the season in the 23rd minute to put Juve in front and committed displays from Blaise Matuidi and Federico Bernardeschi ensured Massimiliano Allegri's men did not miss Paulo Dybala, who was named on the bench after he stormed off the touchline against Parma.
Ronaldo's 18th league goal of the season and a late strike from Can made sure of the Bianconeri's first victory in three matches across all competitions, coming a day after second-placed Napoli were held to a draw by Fiorentina to make a successful title defence look all the more likely.
Juve were given an early scare when Filip Djuricic was allowed a clear run into the box where Wojciech Szczesny brought him down, but the referee judged that the goalkeeper's challenge was legal after consulting VAR.
Szczesny made a good save to deny Manuel Locatelli's rising drive from 20 yards before the visitors took the lead with their first clear chance of the game.
Ronaldo pounced on a poor clearance by Sassuolo keeper Andrea Consigli and started a move that saw his shot from the edge of the box saved before Khedira slotted home the rebound.
Khedira headed narrowly wide on the cusp of half-time and Ronaldo had the ball in the net six minutes into the second half but an offside flag was correctly raised against him.
Sassuolo captain Domenico Berardi missed an open goal from 35 yards when Szczesny fluffed his lines at a clearance, shortly before Khedira failed to turn the ball over the line when Mario Mandzukic presented him with a golden chance just after the hour mark.
Ronaldo rose to meet Miralem Pjanic's corner in the 70th minute, beating Consigli to the ball and sending a glancing header into the far corner.
Can came on for Matuidi and within a minute he made it 3-0, latching onto Ronaldo's unselfish ball across the edge of the Sassuolo box and sliding home a low, angled shot to wrap up a comfortable win.
What does it mean? The Old Lady has one hand on the title
An 11-point lead may well be unassailable for Napoli and Juve successfully eradicated the errors that led them to disappointing results in their previous two games.
Khedira covers for dropped Dybala
Juve might have lacked a creative presence in and around the penalty area with Dybala being dropped but Khedira's all-action display ensured the Argentine playmaker was not missed.
Consigli causes problems
Sassuolo goalkeeper Consigli opted for the spectacular over the sensible with a number of parried saves, and one of them presented Khedira with the chance from which he scored.
Key Opta facts
- Juventus have won all their last seven Serie A games against Sassuolo, with an aggregate score of 21-3.
- Cristiano Ronaldo has scored at least 20 goals (all comps) in all the last 13 seasons (one with Juventus, nine at Real Madrid and three for Manchester United).
- Juventus are unbeaten in their last 24 Serie A away games (W20 D4); only between 2011 and 2012 have they gone longer without a top-flight defeat (25).
- Sami Khedira has scored four Serie A goals against Sassuolo, his joint-record against an opponent in the Italian top-flight (level with Udinese).