Colin Calderwood's side had hoped to extend their lead at the top of League One against one of the division's strugglers, but Orient upset the form book with a classic away performance which saw them repeatedly hit Forest on the break.
Goals from Luke Guttridge and Adam Chambers put the visitors in the driving seat before half-time and after Ian Breckin had pulled one back for the home side, Wayne Corden's spectacular solo strike restored Orient's advantage and ensured they returned to London with all three points for the first time.
Forest named the same team that had demolished Crewe last weekend but this was a very different performance.
While they had torn apart the opposition at Gresty Road with some superb football, against Orient they looked short of ideas and cutting edge.
The visitors too found chances hard to come by but crucially made the most of their opportunities when they arose.
Forest could have few complaints as they went into the interval two goals behind.
The first came following a neat passing move on the edge of the box which culminated in the ball being squared to Gutteridge, who rifled an arrowing finish high into the roof of the net in the 25th minute.
Forest came close to an equaliser on several occasions with Nicky Southall hammering a shot only narrowly high and wide, Kris Commons forcing a decent save from Glyn Garner and Grant Holt seeing the keeper produce an even better stop after he had connected crisply with a Commons cross.
But things were to get worse for the home side as Orient powered further ahead. James Walker seemed to be little threat as he latched on to a long ball wide on the left, but he cut inside and ran at Danny Cullip leaving the defender in his wake. After powering dangerously into the box he cut the ball back to Chambers, who provided a firm low finish into the back of the net.
Forest introduced a fourth striker in the form of Junior Agogo as a half-time substitute but it was Orient who could initially have added to their tally as Walker again tormented Cullip before finding Guttridge with acres of space in the box only for the midfielder to fire wide.
Forest did begin to pile on the pressure, however, and they were soon rewarded. A foul on Commons on the left gave Southall the chance to deliver from a free-kick and he picked out Breckin, who headed a looping effort into the back of the net from eight yards.
But again while they were on top, they could not conjure up much in the way of opportunities.
And Orient ensured that their resistance was short lived as Corden produced a strike of superb individual brilliance to restore their visitors' two-goal advantage.
The former Mansfield Town man raced through two challenges and into the box before bending a fine finish beyond the advancing Paul Smith.