Henson's fellow replacement Andy Saull scored the decisive try with Saracens fly-half Owen Farrell and Wasps' opposite number Dave Walder landing two penalties apiece.
Wasps left Wembley with a bonus point but it was their first Premiership defeat since their 37-10 mauling at home to Northampton in October.
Saracens attracted a Boxing Day crowd of 38,421 to Wembley and all eyes were on Henson, who had not played since the Ospreys' LV= Cup semi-final in March, 2009.
For six months after taking unpaid leave from the Welsh club, Henson believed he would not play rugby again.
The 28-year-old fled Wales following his split from fiancee Charlotte Church and he trod the reality television beat, with appearances in 71 Degrees North and Strictly Come Dancing.
But amid all the sequins and prime television appearances, Henson said he began to miss the blood and thunder of top-flight rugby.
He jumped at the chance of joining Saracens until the end of the season and his sights are set on playing for Wales again, first in the Six Nations and then next year's Rugby World Cup.
Yesterday was a first tentative step down that road. Typically, it took just two minutes before Henson was at the heart of the action when he picked off an interception just metres from the Wasps line.
Henson drove for the line but he was wrapped up by Joe Simpson and could not ground the ball as the Wasps scrum-half denied him a dream comeback.
Despite his limited training time with Saracens, Henson did not shy away from contact and he made a couple of powerful ball carries. One of which left Wasps centre Ben Jacobs shaken.
When Henson came on, Saracens led 10-0. There had almost been more entertainment at half-time than in the whole first 40 minutes, when Saracens supporter Matthew Rouse scooped 250,000 in the crossbar challenge.
Saracens were 3-0 up at the interval courtesy of a penalty from Farrell and they extended their advantage with a beautifully crafted try from Saull six minutes into the second half.
With Saracens on top, Henson was sent on for Michael Tagicakibau and after almost marking his arrival with a try, spent most of his action in defence as Wasps cranked up the pressure and two penalties from Walder drew them back into touching distance.
But Saracens held firm and sealed an important victory.