A scrappy, scoreless opening 20 minutes was brought to life when Wasps' Jake Cooper-Woolley crashed over, before Christian Wade added a second try.
Luke Wallace bundled over for Quins but Nathan Hughes burst through to give the hosts a 21-5 half-time lead.
Thomas Young added a fourth try for the bonus point before Siale Piutau and Brendan Macken crossed late on.
Dai Young's Wasps have not lost in the league since a 15-9 defeat at Sale on 2 January, a run which has seen them climb to third in the table.
Relive Wasps' victory over Harlequins
Their winning sequence included a 64-23 thumping of leaders Saracens on Valentine's Day, but there was little evidence of the fluent, attacking rugby which Wasps have based their game on in recent weeks in the early stages.
However, once prop Cooper-Woolley scored, confidence began to flow. Slick hands from Charles Piutau put Wade in and Hughes made their first-half dominance count with a third.
Charlie Walker's try for Quins made for a nervy few minutes with the lead cut to 11 points, but another fine passing move and some quick feet from Wade put Young in for the bonus point and Siale Piutau beat three defenders to make sure of the win.
Macken capped another fine afternoon for the hosts as he ran through unopposed to complete the scoring.
Wasps, who last won six league games in a row during their Premiership winning season of 2007-08, now hold a five-point lead over fifth-place Northampton Saints.
Wasps director of rugby Dai Young:
"You have to beat Quins off with a big stick, every time you play them, they are always a threat and they're always going to keep coming back at you.
"We lost a bit of that momentum in the first period of the second half but we give Quins a bit of credit for that.
"I was pleased we held out and I thought that fourth try was really important for us."
Harlequins director of rugby Conor O'Shea:
"I have to say, I thought Wasps were outstanding. Sometimes you lose some games and we're very proud people and don't like being on the end of big loss.
"We lost a lot of collisions, and we won a fair few too, but the ones we lost cost us a heck of a lot more and they have a lot of bullets to fire at you.
"They are in a rich vein of form, but we will dust ourselves down and there was no doubting the work ethic going in from our players there.
"We have to make sure we get ourselves right back into it next week, as there are probably six teams fighting for two spots behind the front two."
Wasps: Miller; Wade, C Piutau, S Piutau, Halai; Gopperth, Robson; Mullan (capt), Festuccia, Cooper-Woolley, Cannon, Myall, Young, Smith, Hughes.
Replacements: Johnson, Bristow, Swainston, Rowlands, Rieder, Stevenson, Jackson, Macken.
Harlequins: R. Chisholm; Yarde, Stanley, Sloan, Walker; Botica, Tebaldi; Lambert, Buchanan, Jones, Merrick, Horwill (capt), J. Chisholm, Wallace, Luamanu.
Replacements: Ward, Evans, Sinckler, Matthews, Robinson, Egerton, Swiel, Hopper.
Wasps won a sixth straight Premiership game with a bonus-point victory over Harlequins at the Ricoh Arena.