Giorgos Karagounis last week opened his Fulham account with an exquisite half-volley against Blackpool in the FA Cup and scored another fantastic goal on Saturday, bursting through the middle to unleash a fierce drive that went in off the inside of the post.
However, the Greek veteran's moment of magic was not enough for Fulham as Di Santo ensured Wigan would return to the north west with a point. The Argentina international made the Latics' pressure count in the 71st minute, cutting in from the left before unleashing a fierce drive that beat Mark Schwarzer.
The visitors were quicker to settle, with Shaun Maloney getting a fourth-minute strike away. James McArthur saw a fizzing 20-yard strike fly just over as Wigan returned to the attack, before the Scotland international was denied another shot thanks to fine defensive cover by Bryan Ruiz.
The hosts were struggling to contain the Latics but began to threaten at the other end as Mladen Petric curled a 20-yard free-kick over. Ruiz almost put through Dimitar Berbatov with a fine ball, before Petric lashed over in the 15th minute.
Berbatov was denied by a smart Ivan Ramis block as Fulham continued to press for an opener, which came in some style after 22 minutes. Karagounis picked up the ball 40 yards out and made a beeline for goal, jinking past James McCarthy before rifling home a low strike off the inside of the post.
Alex Kacaniklic mishit a volley when the Whites returned to the attack. The visitors could have levelled as half-time approached as Emmerson Boyce found Di Santo with a fierce right-wing cross, although the Argentina striker could not direct on target.
Maloney found time and space to unleash a fine strike that Schwarzer superbly tipped onto the bar. Di Santo then expertly teed himself up before firing a volley from the edge of the box into the side-netting, leading Fulham boss Jol to bring on former Wigan favourite Hugo Rodallega in place of the ineffective Petric.
There was a goal shortly after the Colombian's introduction, although it was scored by former team-mate Di Santo. The 23-year-old cut in from the left flank and dribbled towards the edge of the box, before unleashing a thumping right-footed effort that beat Schwarzer.
Di Santo struck the side-netting late on, before team-mate Ramis was stretchered off in stoppage time. Maynor Figueroa incredibly cleared a Ruiz strike off the line as Wigan's defence struggled to cope, with the final whistle met by boos from home fans.