It was a game of two halves for Walsall who started brightly and put themselves ahead through Stuart Sinclair.
After going into half-time 1-0 up, the Saddlers capitulated in the second half.
Two minutes in and the home side equalised through Joe Widdowson, before a terrible mix-up for Walsall allowed Josh Wright to put the hosts ahead.
Conor Wilkinson added to the score in the 75th minute, before being sent off in a scuffle with Dan Scarr five minutes later.
Darrell Clarke used the 4-2-3-1 formation for the first time this season, making three changes from the 3-0 loss at home to Salford.
Josh Gordon, Elijah Adebayo and Mat Sadler made way for Danny Guthrie, who returned from injury, Liam Kinsella and Rory Gaffney, who was eligible in the last game against his parent club.
The team selection saw the Saddlers start with Kinsella and Guthrie in holding midfield with Sinclair just ahead of them, while Gary Liddle moved to right-back and James Clarke partnering Dan Scarr at centre-back.
Rory Gaffney started up-front on his own.
Orient boss Ross Embleton made one change from the team that beat Northampton 1-0 in their last league game, with Myles Judd replacing Sam Ling at left-back - as Ling dropping out of the squad altogether.
The O’s started in a 4-3-1-2 formation.
Walsall started the game brightly with Sinclair keen to assist Gaffney up-front. The midfielder was making runs off the tall striker and giving the away side an extra option from deep.
After some earlier pressure from Walsall, Orient began to play - with both sides looking dangerous in the opening 10 minutes but without any clear-cut chances.
The opening goal, however, almost came from an unlikely source. Winger Wes McDonald fed Zak Jules who swung in a low cross from the left. It was deflected and almost snuck in at the near post, but Dean Brill made a strong save in the Orient goal.
The home side almost took the lead themselves after Jules gave away a free-kick on the edge of the penalty area. It was taken by Josh Wright who lifted it over the wall and just wide of the post.
The momentum was truly with The O’s as they continued to go close. Wright again was the man but a low cross was just behind him when he had the goal gaping from five yards.
Moments later an Orient corner was headed back across goal and cleared off the line from Gaffney.
But it was Walsall who took the lead in the capital. McDonald played a delightful flick around the corner to set Jules rampaging towards the byline. His low cross is initially saved but after a scramble it pops up to Sinclair who taps it home.
Orient almost responded immediately, however, when Matt Harrold was played in on goal and placed the ball into the bottom corner - to find the assistant referee had waved his flag for offside.
With five minutes left of the half, Walsall almost doubled their lead through captain Clarke. A Guthrie corner was met by Jules who headed it down across goal, Clarke was stretching and his touch on the ball was straight at the goalkeeper from close range.
An entertaining and relatively even first half came to an end with Walsall winning 1-0.
Within minutes of the restart, however, Orient were level. Some excellent last ditch defending from Kinsella managed to prevent the home side getting a shot away, but the ball fell kindly to Joe Widdowson who curled it into the top corner from the edge of the box.
On the hour mark, Orient put themselves ahead after a terrible mix-up from Walsall.
Kinsella plays a harmless ball back to Guthrie who lets it run behind him. It’s picked up by Orient who raced through on goal and the ball is squared to Harrold who put The O’s ahead.
The home side continued to put pressure on the Walsall defence as Darrell Clarke made a tactical change to get his side back in the team. He changed his side to a 3-4-3 formation, with Liddle moving to centre-back. Jules and Norman operated as wing-backs and Adebayo, Gordon and Gaffney played as a front three.
But by the 75th mark Orient had increased their lead, scoring a third. Conor Wilkinson picked the ball up on the right, he cut inside unchallenged and his scuffed shot trickled into the net.
Five minutes later, goalscorer Wilkinson was given a red card for a moment of madness. In a melee with Scarr, the striker grabs the defender by the throat and is deservedly given his marching orders.
Although Walsall had all of the ball in the final minutes of the game, it fizzled out with no clear chances and the game finished 3-1 to the home side.
Walsall: Roberts, Liddle, Clarke, Scarr, Jules, Holden (Adebayo 67), Guthrie (Norman 63), Sinclair, Kinsella, McDonald (Gordon 67), Gaffney.
Subs not used: Rose, Sadler, Bates, Hardy.
Leyton Orient: Brill, Widdowson, Gorman (Marsh 67), Coulson, Clay, Wilkinson, Judd, Happe, Brophy (Dayton 90), Harrold (Alabi 83), Wright.
Subs not used: Sargeant, Maguire-Drew, Dennis, Ogie.
Attendance: 6,951 (852 Walsall).