Richie Foran and Billy McKay scored the goals in the first half at the Tulloch Caledonian Stadium as Terry Butcher's men made it three wins from as many games.
Caledonian Thistle scored after just four minutes when Foran spun off his marker to meet a Graeme Shinnie free-kick and send a diving-header past Lee Hollis.
Aaron Doran created the opening for the second on 36 minutes with a superb pass to split the Motherwell defence, allowing David Raven to set up McKay to slot into the net from close range.
Moments after the opening goal James Vincent almost doubled the lead, but a timely deflection off Stephen McManus diverted the shot narrowly over the crossbar following good work by Doran.
Despite their lacklustre start to the game, the visitors almost levelled when Iain Vigurs set up Keith Lasley, but the Motherwell skipper's fierce drive from 12 yards was turned away by Thistle keeper Dean Brill at his near post.
Vincent was inches away from scoring with a spectacular volley from the edge of the area as he latched on to McKay's flick shortly before the interval.
Motherwell spurned a great chance to get back into the game in the second half when Brill misjudged Vigurs' corner, only for Shaun Hutchinson to send his header onto the roof of the net.
The visitors felt they should have had a penalty when Raven appeared to catch Vigurs from behind, but referee Iain Brines was not interested.
Doran was denied by Hollis as the game entered its final 10 minutes and from the resultant corner Foran prodded an effort narrowly wide at the back post.