The US national team star notched an excellent assist on the opener and forced an own-goal from the 'keeper on the winner as Spurs punched their ticket to the last 32 with a 3-1 win on the final matchday in Group J.
Dempsey's splitting pass sent Emmanuel Adebayor in alone to break the ice near the half-hour. Just before departing in the 80th minute, Deuce's bullet header from a restart caromed off the bar and then the back of away netminder Orestis Karnezis to put Spurs up to stay.
Friedel, meanwhile, registered four saves in his first European start in more than four years. His last trip to the knockout stages came in the 2006-07 UEFA Cup with Blackburn Rovers, while Dempsey is back after a run to the Europa League final with Fulham in 2010.
Over in Group L, Alejandro Bedoya netted the winner in Helsingborg's 3-1 victory at FC Twente. With both sides already eliminated before the night began, the US midfielder fired home a loose ball in the 21st minute for his second goal in the last three group matches.
Elsewhere, Steve Cherundolo came on for the final 19 minutes to help Hannover 96 finish top in the group with a 2-2 draw at Levante. The skipper was kept out of the lineup with the Reds already qualified to the knockouts, but was brought on to solidify the back to clinch first place over the Spaniards by a point.
Group E action saw Josh Gatt and last-place Molde FK go home on a high after winning 1-0 at Stuttgart. The winger worked 68 minutes as the Norwegian champs pulled off an impressive sweep of the Bundesliga giants.
In Group K, Mikkel Diskerud worked a solid shift as Rosenborg ended up a distant third with 1-0 loss at Bayer Leverkusen. Compatriot David Yelldell served as backup goalkeeper for the hosts.
Terrence Boyd came on for the final quarter-hour as cellar-dwellers Rapid Vienna finished up with a 1-0 victory over group winners Metalist Kharkiv.