Tammy Abraham and Cesar Azpilicueta scored first-half goals as Frank Lampard's men bounced back from their weekend defeat to Everton by sewing up second spot in Group H.
The hosts knew three points would confirm their place in the last 16 and encountered little resistance until former Chelsea forward Loic Remy netted a 78th-minute consolation for the bottom-placed French side.
Valencia's victory over Ajax in Amsterdam denied Chelsea top spot, but Lampard will be satisfied after becoming the first Englishman to oversee the entirety of a successful group-stage campaign since Harry Redknapp, his uncle, did so with Tottenham in 2010-11.
Chelsea almost scored three times, with Christian Pulisic and Emerson Palmieri threatening, before Abraham notched his second European goal in the 19th minute.
Willian darted past Lille left-back Jeremy Pied and squared for the unmarked striker to apply a simple finish.
The lively Emerson tested Mike Maignan a second time and then supplied the corner that Azpilicueta headed home 10 minutes before half-time.
Maignan needed attention following a collision with Kurt Zouma but his good form continued with a double save from Pulisic and Willian upon the resumption.
The 24-year-old goalkeeper was eventually forced from the field with an ice pack applied to his knee in the 72nd minute.
Leo Jardim, Maignan's replacement, saved from Mateo Kovacic, and it was at the other end that the next goal arrived, Remy firing in after substitute Jonathan Bamba found space in the box.
It proved a minor hiccup for Chelsea, who held their nerve en route to a first Champions League home win in six matches.
What does it mean? Blues a threat to Champions League challengers
Chelsea will find it tougher against more qualified opponents in the next round but the team that draws them are unlikely to relish the challenge.
Willian, Abraham and Pulisic can be a real handful going forward, while Antonio Rudiger's return from a lengthy groin injury brought stability at the back.
Creative Willian leads way for Chelsea
No player has more assists in European competitions since the start of last season than Willian, who registered an eighth when he set up Abraham and was deserving of a goal himself.
Maia goes missing for Lille
Lille lost the battle in midfield, giving up almost 65 per cent of possession, and got little help from Thiago Maia, an ineffectual figure as he lost each of his six duels and completed just six passes in over an hour on the pitch.
Chelsea will discover their last-16 opponents when the draw takes place in Nyon on Monday.
Before then comes Saturday's Premier League home game against Bournemouth, while Lille must regroup ahead of their Ligue 1 meeting with Montpellier.