After a goalless first period, that man Simpson scored his 21st of the season to put Orient in front and loanee Calaum Jahraldo-Martin added a late second to seal an impressive victory.
The O’s started the game with a 4-2-3-1 formation with top scorer Simpson just behind Palmer, while new signing Nigel Atangana and Jack Payne were the deep-lying midfielders.
The first chance of the game went the way of the hosts when Atangana gave away a free-kick just outside the box, but the effort from Thompson was well over the bar, while Sam Wood was also off target with an effort from distance.
Opportunities were few and far between in the opening half an hour, and though Wycombe had a large amount of possession, Cisak was rarely troubled in the O’s goal.
Orient did create a half chance with 26 minutes on the clock when a ball through almost presented Simpson with an opportunity but Chairboys goalkeeper Alex Lynch came out and gathered.
Loanee Calaum Jahraldo-Martin then helped the momentum turn in the visitors favour with a couple of neat runs, however, at the end of his second a weak shot was easily collected by Lynch.
The tide had turned in the O’s favour and a McAnuff free-kick on 35 minutes found the head of Palmer, but his glancing effort was wide of the target.
Atangana was having a very solid debut in the middle of the park and only a superbly timed intervention denied Luke O’Nien an attempt on goal.
The game had begun to open up and strong penalty appeals were waved away by referee Bond, Darren Bond, when Palmer went down in the box just shy of the 40-minute mark.
The O’s were on the front foot and a lovely free-flowing move across the park for the O’s ended with Shaw creating an opening for Jahraldo-Martin whose fierce shot was tipped over by Lynch, only for the referee to award a goal-kick.
Orient were on top as the half came to a close, and Payne was able to get a ball in from the left by-line though no O’s forward was able to get on the end of it.
The half-time break changed very little as Nolan’s side started the second period on the front as a ball in from McAnuff down the left found the head of Palmer. He nodded the ball into the path of Simpson and his turn and shot was blocked.
Cheered on by 805 Orient fans who made the journey to Adams Park, E10 the O’s remained in control and a period of pressure resulted in Simpson getting a shot away but it was off target.
After a lively start to the second half, the game went through a quiet spell, and despite the chances – both goalkeepers were yet to be called into action.
But the next touch for the Wycombe goalkeeper Lynch was to pick the ball out of his net in the 65th minute.
A ball into the box was headed on by skipper Baudry and the prolific Simpson had plenty of time to take a touch before smashing home his 21st goal of the season and put Orient into a deserved lead.
The visitors tried to build and an opening was found by McAnuff however his low left-footed effort from just outside the box was wide of the target.
The impressive Atangana was forced off through injury with 19 minutes remaining, and replaced by Bradley Pritchard. A second strike was looking more likely than an equaliser and a lofted ball into the box was nodded on by Baudry only for Lynch to gather under pressure from Palmer.
Wycombe did work an opening as the game entered the final 10 minutes, when a ball in from the right was flicked goalwards by substitute Gozie Ugwu, but the effort was wide of Cisak’s right-hand post.
Gareth Ainsworth’s side had upped the ante for the final 10 minutes and defender Aaron Pierre rose tallest in the box to head an effort goalwards, however, Pritchard was on the line to keep the effort out and the O’s lead intact.
As time began to tick away Jacobson had an opening for the hosts but after cutting in off the left, his right-footed shot was way off target and failed to trouble Cisak in the Orient goal.
But it was Orient who went on to seal the win with a minute remaining with a counter attack at its finest.
The O’s broke away and the pace of Jahraldo-Martin left Wycombe backtracking. His pinpoint ball found the run of Simpson, who returned the compliment for the onrushing Jahraldo-Martin and he kept his cool to slot past Lynch.
There was almost time for a third when McAnuff cut in from the left and his pull back found substitute Armand Gnanduillet and his effort took a deflection on the way behind for a corner.
WYCOMBE: Lynch, Jombati, Stewart, Pierre, Jacobson, Harriman (Udumaga 83), McCarthy, O’Nien, Wood, Hayes (C) (Cowan-Hall 57), Thompson (Ugwu 71)
SUBS: Richardson, McGinn, Bean, Kretzschmar
BOOKINGS: Jombati (76)
ORIENT: Cisak, Clohessy, Baudry (C), Essam, Shaw, Jahraldo-Martin, Atangana (Pritchard 72), Payne, McAnuff, Simpson, Palmer (Gnanduillet 80)
SUBS: Grainger, Kpekawa, Nolan, Turgott, Kashket
GOALS: Simpson (64), Jahraldo-Martin (89)
BOOKINGS: Jahraldo-Martin (90)
REFEREE: Darren Bond
ATTENDANCE: 4,432 (805 Orient supporters)