With the season not quite at the halfway point, Lyon already look set to become the first club from a major European league to win six titles in succession.
They have 49 points from a maximum 54 after 18 games, with Lens still on 32 points.
"We wanted to show that we are stronger than last season", said Lyon coach Gerard Houllier. "I think we are. We're more mature and stronger mentally, particularly in important matches."
Juninho opened the scoring for the visitors from a free kick after 23 minutes before setting up Florent Malouda with a fine ball for Lyon's second goal 11 minutes later.
With Fred, John Carew and Karim Benzema all sidelined with injuries, Lyon coach Gerard Houllier took a gamble by fielding midfielder Malouda up front and it paid off.
Brazil defender Cris made it 3-0 five minutes into the second half, following up after Lens keeper Charles Itandje had failed to block a Malouda attempt.
Twelve minutes later, Juninho was on target again, wrapping up the victory from the edge of the box.
Lens had started the top-of-the-table clash in promising fashion but Lyon took control after moving ahead and never let go.
"I think they'll win the Champions League," said Lens president Gervais Martel. "One draw and one defeat after 18 (Ligue 1) games is just amazing. Nobody else in Europe has done that."
Troubled Paris St Germain were held to a 0-0 home draw by fellow strugglers Nice in a tense match earlier on Sunday.
The Paris club, playing their first home league game since one of their fans was killed by a policeman last month, kept trying but failed to breach a tight Nice defence.
PSG stay 15th with 18 points from 17 games while Nice remain in 17th place two points back after 18 matches.
The Parisians, whose 4-0 UEFA Cup win over Panathinaikos on Wednesday had suggested they were improving, looked nervous against opponents desperate not to lose.
Some 2,000 police were on duty around Parc des Princes, which was half empty with the lower section of one stand still closed after violence flared up following last month's UEFA Cup defeat by Hapoel Tel Aviv. No incidents were reported on Sunday.
Auxerre stayed 13th but moved six points away from the danger zone with a 2-1 win over Lorient in Sunday's other match.
(Additional reporting by Pierre Savary in Lens)