Andrea Dossena gave the O's the early lead and David Mooney doubled their advantage from the penalty spot as Liam Kelly was adjudged to have fouled Jobi McAnuff in the area.
Latics responded well in the second half and had a golden opportunity to pull a goal back through Jonathan Forte but his penalty kick was saved.
Athletic huffed and puffed but were caught on the counter attack deep into added on time and Jay Simpson rounded off the scoring as Latics drop to ninth in Sky Bet League One.
Latics got off to the worst possible start, falling behind in the opening three minutes.
Romain Vincelot's through ball found the onrushing Dossena and he confidently placed the ball past Jake Kean from the left-hand side to put the O's ahead.
Latics responded well as Carl Winchester set off on a mazy run, taking on three but was denied finally by the last defender.
Athletic dominated the possession stats but were struggling to calve a way past the stubborn Orient defence.
The home side looked threatening on the break and could have been awarded a penalty on 15 minutes but the referee waved away the protests.
Latics were forced into a change soon after as Genserix Kusunga replaced George Elokobi who went off with injury.
Midway through the first half, Leyton Orient doubled their lead from the penalty spot.
Jobi McAnuff was hauled to the ground in the box by Liam Kelly and Mooney stepped up to send Kean the wrong way and extend the home side's lead.
The home side needed a response but a number of set pieces were cleared up by former Latics goalkeeper Alex Cisak
Whilst Latics attacked, the O's looked promising on the counter attack and ten minutes before the break, Ryan Hedges delivered a teasing ball into the box which just evaded the onrushing Mooney.
Five minuets from the break, Latics' best chance of the half fell to winger Rhys Turner.
The 19-year-old found space at the back post after Mills' cross found the youngster but he could only hit his half volley over the crossbar.
Latics were forced into another change at the start of the second half as Connor Brown replaced Joseph Mills and they started the second half much more positively.
Brown cut inside and fed Danny Philliskirk but the forward rushed his shot and it ended up in the stands.
Only minutes later, Winchester's persistence and cross caused O's goalkeeper Cisak to clear for a corner. The resulting corner was cleared to the Northern-Irishman who struck too high and the chance passed.
Latics had the urgency and looked the more likely of the two sides to get the next goal.
Rhys Murphy entered the field on the hour mark and made an instant impact, winning a penalty for Athletic on 64 minutes.
He was bundled to the floor by Mathieu Baudry and Forte stepped up only for Cisak to save and Kelly's follow-up smashed against the crossbar.
Only a minute after the penalty miss, Poleon drifted around his defender and unleashed a shot but the linesman's flag prevented the attack from continuing.
Latics had to be wary of the home side on the counter attack as Chris Dagnell found acres of space behind the defence 20 minutes from time but he miscontrolled and the visitors breathed a huge sigh of relief.
Forte almost made amends for his penalty miss soon after but he could only drag his shot wide after working a good opportunity for himself.
Athletic were attacking in numbers but were met by a stubborn O's defence which thwarted the attacks.
The visitors threw everything forward in a bid to get something out of the game but were caught on the counter attack deep into additional time as Orient killed off the game.
Substitute Simpson found space in the area and fired past Kean to consign Latics to a heavy defeat at the hands of the league's bottom side.
Leyton Orient: Cisak, Sawyer, Lowry, Baudry, Dossena, McAnuff (Cox 61'), Wright, Vincelot, Hedges (Simpson 80'), Mooney (Bartley 70'), Dagnall.
Subs not used: Lisbie, Clarke, Grainger, Plasmati.
Oldham Athletic: Kean, B.Wilson, J.Wilson, Elokobi (Kusunga 17'), Mills (Brown 46'), Kelly, Winchester, Turner (Murphy 58'), Philliskirk, Forte, Poleon.
Subs not used: Coleman, Lockwood, Dieng, Mellis.
Goals: Leyton Orient (Dossena 3', Mooney 25', Simpson 90+5') 3-0 Oldham Athletic
Attendance: 4,423 (544 visiting supporters)