Spirit – who were already out of the competition – posted 142 for six with Adam Rossington hitting a quick-fire 46 from 29 balls and Captain Eoin Morgan unbeaten on 22 off 16 deliveries.
In response, Originals were reeling at 21 for three but Colin Ackermann’s 53 off 40 balls led the home side’s recovery.
With nine needed from five deliveries, Spirit debutant Brad Wheal – who took a brilliant four for 17 – held his nerve with some fine death bowling.
Originals remain fifth in the table and one point away from the top-three qualification places, with Spirit still bottom, despite the win.
London Spirit: 142/6 in 100 balls (Rossington 46, Morgan 22 n.o, Hartley 3/27)
Manchester Originals: 136/9 in 100 balls (Ackermann 53, Wheal 4/17, Cullen 2/19). (BBC)