Fresh from their midweek draw with Barclays Premier League leaders Manchester United, the hosts scored once in either half to leave Wigan in the relegation zone and put another dent in the FA Cup finalist's survival bid.
A first Upton Park goal for Matt Jarvis and a Kevin Nolan volley secured the win which moved Sam Allardyce's side into the top 10, although they were second best for much of the second half with the Latics unable to make their dominance pay.
Wigan started brightly and were the first side to create an opening as Antolin Alcaraz - who was replaced after 15 minutes due to injury - fired a low shot straight at Jussi Jaaskelainen.
Hammers skipper Nolan had found the net just once since the turn of the year before Saturday, but he had two half chances to open the scoring as the hosts came back into the game.
Firstly he could not rise high enough to make meaningful contact with a Gary O'Neil corner that had been flicked into his path by James Collins before latching onto a free-kick and seeing his volley pushed clear by Wigan goalkeeper Joel Robles.
Dead ball specialist Shaun Maloney put a 22-yard free-kick just over Jaaskelainen's bar with both sides still in search of the opening goal.
It came just four minutes later when Jarvis' cross from the left flank evaded both Mohamed Diame and Nolan before sneaking inside Robles' far post.
West Ham then had strong claims for a penalty following an exchange of passes between Ricardo Vaz Te and Nolan, with James McCarthy appearing to trip Nolan as he prepared to shoot.
Andy Carroll, such a thorn in the side of the Manchester United defence on Wednesday evening, was embroiled in a tussle with Wigan captain Gary Caldwell resulting in both men being shown a yellow card by referee Neil Swarbrick.
With half-time approaching Wigan were struggling to keep possession as well as they had when the scores were level and both Collins and Diame had shots blocked after the Latics' defence fell asleep at a quickly-taken West Ham free-kick.
Roberto Martinez made his second change at half-time as he introduced James McArthur in place of Callum McManaman.
The visitors came out attacking with both Jordi Gomez and Arouna Kone having strikes at Jaaskelainen's goal within two minutes of the re-start.
Wigan continued to press but could not work a clear opening on West Ham's goal, with the hosts fairing little better when they ventured forward.
Diame saw a dipping effort gathered by Robles just before the hour-mark before Joe Cole made his return from a hamstring injury, replacing Ricardo Vaz Te on the wing.
Wigan finally created a decent opportunity as Maynor Figueroa lofted a ball over the West Ham defence and Emmerson Boyce's diving header was kept out by Jaaskelainen.
That effort seemed to galvanise Martinez's side and they dominated for the next 15 minutes, culminating with substitute McArthur forcing a smart save out of the Finnish goalkeeper with 20 minutes remaining.
Paul Scharner then headed straight at Jaaskelainen when free inside the area with the home fans starting to show their tension as their fragile lead continued to be threatened.
But those worries were put to bed with a little over 10 minutes remaining as Nolan latched on to Carroll's pass to volley West Ham into a two-goal lead and score his seventh goal of the season.
Carroll should have added a third himself after bursting into the area but he put his shot wide.
With all of the teams above Wigan picking up points the defeat in east London means Martinez's side are three points adrift of safety with just five games remaining.